3,4-dihydro-2H-chromen-4-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A 90 g (0.60 mole) portion of 4-chromanamine and 450 ml of ethanol were placed in a 2-l, 3-necked flask, equipped with a stirrer and reflux condenser fitted with a drying tube, and treated with 75 g (0.61 mole) of salicylaldehyde. The reaction mixture was refluxed for 8 hrs., stored overnight at room temperature, cooled and filtered. The yellow crystalline solid was washed with 150 ml of ethanol, ether and dried; m.p. 123°-126°. Yield: 126 g (83%). equipped with a stirrer reflux condenser fitted with a drying tube The reaction mixture was refluxed for 8 hrs cooled filtered The yellow crystalline solid was washed with 150 ml of ethanol, ether dried

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

Procedure: A 90 g (0.60 mole) portion of 4-chromanamine and 450 ml of ethanol were placed in a 2-l, 3-necked flask, equipped with a stirrer and reflux condenser fitted with a drying tube, and treated with 75 g (0.61 mole) of salicylaldehyde. The reaction mixture was refluxed for 8 hrs., stored overnight at room temperature, cooled and filtered. The yellow crystalline solid was washed with 150 ml of ethanol, ether and dried; m.p. 123°-126°. Yield: 126 g (83%). equipped with a stirrer reflux condenser fitted with a drying tube The reaction mixture was refluxed for 8 hrs cooled filtered The yellow crystalline solid was washed with 150 ml of ethanol, ether dried

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

Procedure: A solution of chroman-4-ylamine (2.550 g, 17.09 mmol) in AcOH (50 mL) at RT was treated with Br2 (3.01 g, 0.96 mL, 18.8 mmol) drop-wise. The reaction was stirred at RT until HPLC analysis showed complete consumption of starting material. The mixture was diluted with H2O (100 mL) and NaOH was added until the solution became basic. The aqueous layer was extracted with EtOAc until TLC analysis of the aqueous layer showed no evidence of the title compound. The combined organics were dried over MgSO4 and concentrated in vacuo to yield the crude compound, which was purified by flash column chromatography to afford the pure title compound. MS (APCI pos) 229 (M+H). consumption of starting material The mixture was diluted with H2O (100 mL) and NaOH was added until the solution The aqueous layer was extracted with EtOAc until TLC analysis of the aqueous layer The combined organics were dried over MgSO4 concentrated in vacuo to yield the crude compound, which was purified by flash column chromatography

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

Procedure: The titled compound was synthesized according to the procedure described for preparation of N4-cyclopentyl-5,6-dimethyl-N2-(pyridin-2-ylmethyl)pyrimidine-2,4-diamine (Example 29) using 3,4-dihydro-2H-chromen-4-ylamine instead of cyclopentanamine. The crude material was purified by column chromatography eluting with mixture of chloroform/ethanol/20% water solution of ammonia (200:10:1), and then the final product was washed with diethyl ether to afford the titled compound as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.89 (s, 3H), 2.10 (bs, 1H), 2.42 (s, 3H), 4.11 (bs, 1H), 4.27 (bs, 1H), 4.93 (bs, 1H), 5.04 (bs, 1H), 5.31 (bs, 1H), 5.48 (bs, 1H), 6.75-6.88 (m, 3H), 7.20 (bs, 1H), 7.27 (bs, 1H), 7.42 (bs, 1H), 7.74 (bs, 1H), 8.02 (bs, 1H), 8.59 (bs, 1H), 10.63 (bs, 1H); MS (ESI) m/z 362.9 (M+1)+. The titled compound was synthesized The crude material was purified by column chromatography eluting with mixture of chloroform/ethanol/20% water solution of ammonia (200:10:1) the final product was washed with diethyl ether