(1R,2S,3R,4R)-2,3-DIHYDROXY-4-(HYDROXYMETHYL)-1-AMINOCYCLOPENTANE HYDROCHLORIDE

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (1R,2S,3R,4R)-2,3-Dihydroxy-4-(hydroxylmethyl)-1-aminocyclopentan hydro-chloride (70.0 g, 380 mmol) was dissolved in water (660 ml) and FmocOSU (N-(9-Fluorenylmethoxycarbonyloxy)-succinimid) (148.5 g, 440 mmol) solved in dioxan (2.00 l) was added. Then saturated sodium hydrogencarbonate solution (800 ml, 880 mmol) was added slowly. The mixture was stirred 3 h at room temperature until TLC (Silicagel Merck 60, chloroform/methanol/acetic acid 8:2+0.1% v/v/v) showed complete consumption of the educts. The obtained precipitate was filtered off and the filtrate was added to water (6.00 l). The resulting suspension was stirred for 5 min and then stored 12 h at 4° C. The resulting suspension was filtered. The obtained solid was washed with cold water (3.00 l) and dried 12 h under reduced pressure at 45° C. over calcium chloride. For a further purification the crude product was suspended in ethylacetate, stirred 1 h, filtered and dried under reduced pressure yielding 134 g (95%) of the title compound as white solid. was added consumption of the educts The obtained precipitate was filtered off the filtrate was added to water (6.00 l) stored 12 h at 4° C The resulting suspension was filtered The obtained solid was washed with cold water (3.00 l) dried 12 h under reduced pressure at 45° C. over calcium chloride For a further purification the crude product stirred 1 h filtered dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol hydrochloride (16.9 g, 45.1 mmol) and 4,6-dichloropyrimidin-5-amine (5.7 g, 35 mmol) in ethanol (45 mL) was evenly distributed amongst three tubes and subjected to microwave conditions (CEM apparatus, 300 W max, 150° C. max, 250 psi max, 3 min ramp, 30 min hold) to afford brown solutions; HPLC/LC MS indicated conversion to the desired product. The three reaction mixtures were combined and concentrated in vacuo to afford the crude title compound as a dark brown oil, which was concentrated from toluene (2×30 mL) and carried on without purification: MS (ESI+) for C10H15ClN4O3 m/z 275.0 (M+H)+; MS (ESI−) for C10H15ClN4O3 m/z 273.0 (M−H)−. subjected to microwave conditions (CEM apparatus, 300 W max, 150° C. max, 250 psi max, 3 min ramp, 30 min hold) to afford brown solutions

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4,6-dichloro-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-1,3,5-triazin-2-amine (735 mg, 2.61 mmol), (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol hydrochloride (400. mg, 218 mmol), potassium carbonate (602 mg, 4.36 mmol) and 1,4-dioxane (3.60 mL) in a sealed tube was heated to 150° C. for 20 mins using MWI. Silica gel chromatography eluting with a gradient of 2 to 7% MeOH in DCM afforded the title compound as a white solid (750. mg, 88%). LC/MS: Rt=1.42 min, ES+ 392 (FA standard). Silica gel chromatography eluting with a gradient of 2 to 7% MeOH in DCM

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol hydrochloride (200 mg, 1.09 mmol), 4,6-dichloropyrimidine (240. mg, 1.61 mmol) and Et3N (0.380 mL, 2.73 mmol) in EtOH (3.00 mL) was heated to 150° C. for 15 min using MWI. The crude mixture was purified via silica gel chromatography eluting with a gradient of 0 to 15% MeOH in DCM to afford the title compound (255 mg, 90%). LC/MS: Rt=1.13 min, ES+ 260. (AA standard). The crude mixture was purified via silica gel chromatography eluting with a gradient of 0 to 15% MeOH in DCM

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (1R,2S,3R,4R)-2,3-Dihydroxy-4-(hydroxylmethyl)-1-aminocyclopentan hydro-chloride (70.0 g, 380 mmol) was dissolved in water (660 ml) and FmocOSU (N-(9-Fluorenylmethoxycarbonyloxy)-succinimid) (148.5 g, 440 mmol) solved in dioxan (2.00 l) was added. Then saturated sodium hydrogencarbonate solution (800 ml, 880 mmol) was added slowly. The mixture was stirred 3 h at room temperature until TLC (Silicagel Merck 60, chloroform/methanol/acetic acid 8:2+0.1% v/v/v) showed complete consumption of the educts. The obtained precipitate was filtered off and the filtrate was added to water (6.00 l). The resulting suspension was stirred for 5 min and then stored 12 h at 4° C. The resulting suspension was filtered. The obtained solid was washed with cold water (3.00 l) and dried 12 h under reduced pressure at 45° C. over calcium chloride. For a further purification the crude product was suspended in ethylacetate, stirred 1 h, filtered and dried under reduced pressure yielding 134 g (95%) of the title compound as white solid. was added consumption of the educts The obtained precipitate was filtered off the filtrate was added to water (6.00 l) stored 12 h at 4° C The resulting suspension was filtered The obtained solid was washed with cold water (3.00 l) dried 12 h under reduced pressure at 45° C. over calcium chloride For a further purification the crude product stirred 1 h filtered dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (1R,2S,3R,4R)-2,3-Dihydroxy-4-(hydroxylmethyl)-1-aminocyclopentan hydro-chloride (70.0 g, 380 mmol) was dissolved in water (660 ml) and FmocOSU (N-(9-Fluorenylmethoxycarbonyloxy)-succinimid) (148.5 g, 440 mmol) solved in dioxan (2.00 l) was added. Then saturated sodium hydrogencarbonate solution (800 ml, 880 mmol) was added slowly. The mixture was stirred 3 h at room temperature until TLC (Silicagel Merck 60, chloroform/methanol/acetic acid 8:2+0.1% v/v/v) showed complete consumption of the educts. The obtained precipitate was filtered off and the filtrate was added to water (6.00 l). The resulting suspension was stirred for 5 min and then stored 12 h at 4° C. The resulting suspension was filtered. The obtained solid was washed with cold water (3.00 l) and dried 12 h under reduced pressure at 45° C. over calcium chloride. For a further purification the crude product was suspended in ethylacetate, stirred 1 h, filtered and dried under reduced pressure yielding 134 g (95%) of the title compound as white solid. was added consumption of the educts The obtained precipitate was filtered off the filtrate was added to water (6.00 l) stored 12 h at 4° C The resulting suspension was filtered The obtained solid was washed with cold water (3.00 l) dried 12 h under reduced pressure at 45° C. over calcium chloride For a further purification the crude product stirred 1 h filtered dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol hydrochloride (16.9 g, 45.1 mmol) and 4,6-dichloropyrimidin-5-amine (5.7 g, 35 mmol) in ethanol (45 mL) was evenly distributed amongst three tubes and subjected to microwave conditions (CEM apparatus, 300 W max, 150° C. max, 250 psi max, 3 min ramp, 30 min hold) to afford brown solutions; HPLC/LC MS indicated conversion to the desired product. The three reaction mixtures were combined and concentrated in vacuo to afford the crude title compound as a dark brown oil, which was concentrated from toluene (2×30 mL) and carried on without purification: MS (ESI+) for C10H15ClN4O3 m/z 275.0 (M+H)+; MS (ESI−) for C10H15ClN4O3 m/z 273.0 (M−H)−. subjected to microwave conditions (CEM apparatus, 300 W max, 150° C. max, 250 psi max, 3 min ramp, 30 min hold) to afford brown solutions

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol HCl (1.00 g, 5.44 mmol) and 2-amino-4,6-dichloropyrimidine (0.982 g, 5.99 mmol) in isopropyl alcohol (8 mL) was added Et3N (1.90 mL, 13.6 mmol). The reaction was heated to 90° C. for 1 h in an oil bath then cooled, filtered and concentrated in vacuo. The residue was dissolved in CH2Cl2 and purified by flash chromatography (20 to 50% MeOH/CH2Cl2) to afford the title compound as an off-white solid (2.025 g, >99%). LC/MS: Rt=0.81 min ES 260 (FA standard). then cooled filtered concentrated in vacuo The residue was dissolved in CH2Cl2 purified by flash chromatography (20 to 50% MeOH/CH2Cl2)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4,6-dichloro-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-1,3,5-triazin-2-amine (735 mg, 2.61 mmol), (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol hydrochloride (400. mg, 218 mmol), potassium carbonate (602 mg, 4.36 mmol) and 1,4-dioxane (3.60 mL) in a sealed tube was heated to 150° C. for 20 mins using MWI. Silica gel chromatography eluting with a gradient of 2 to 7% MeOH in DCM afforded the title compound as a white solid (750. mg, 88%). LC/MS: Rt=1.42 min, ES+ 392 (FA standard). Silica gel chromatography eluting with a gradient of 2 to 7% MeOH in DCM

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol hydrochloride (200 mg, 1.09 mmol), 4,6-dichloropyrimidine (240. mg, 1.61 mmol) and Et3N (0.380 mL, 2.73 mmol) in EtOH (3.00 mL) was heated to 150° C. for 15 min using MWI. The crude mixture was purified via silica gel chromatography eluting with a gradient of 0 to 15% MeOH in DCM to afford the title compound (255 mg, 90%). LC/MS: Rt=1.13 min, ES+ 260. (AA standard). The crude mixture was purified via silica gel chromatography eluting with a gradient of 0 to 15% MeOH in DCM

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4,6-dichloro-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-1,3,5-triazin-2-amine (735 mg, 2.61 mmol), (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol hydrochloride (400. mg, 218 mmol), potassium carbonate (602 mg, 4.36 mmol) and 1,4-dioxane (3.60 mL) in a sealed tube was heated to 150° C. for 20 mins using MWI. Silica gel chromatography eluting with a gradient of 2 to 7% MeOH in DCM afforded the title compound as a white solid (750. mg, 88%). LC/MS: Rt=1.42 min, ES+ 392 (FA standard). Silica gel chromatography eluting with a gradient of 2 to 7% MeOH in DCM

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol hydrochloride (2.00 mg, 1.09 mmol), 4,6-dichloropyrimidine (240. mg, 1.61 mmol) and Et3N (0.380 mL, 2.73 mmol) in EtOH (3.00 mL) was heated to 150° C. for 15 min using MWI. The crude mixture was purified via silica gel chromatography eluting with a gradient of 0 to 15% MeOH in DCM to afford the title compound (255 mg, 90%). LC/MS: Rt=1.13 min, ES+ 260. (AA standard). The crude mixture was purified via silica gel chromatography eluting with a gradient of 0 to 15% MeOH in DCM