tert-butyl 4-aminoazepane-1-carboxylate

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: 4-Amino-1-tert-butyloxycarbonylazacycloheptane colourless oil; RF : 0.36 (alumina; methylene chloride/methanol=9:1)

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: Prepared analogously to example 1.4 from 4-{4-fluoro-2-[(S)-(tetrahydro-furan-3-yl)oxy]-phenylamino}-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid and 4-amino-azepane-1-carboxylic acid tert-butyl ester.

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

Procedure: Prepared analogously to example 1.4 from 4-{4-fluoro-2-[(S)-(tetrahydro-furan-3-yl)oxy]-phenylamino}-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid and 4-amino-azepane-1-carboxylic acid tert-butyl ester.

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

Procedure: The title compound was synthesized from 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-N—Boc-hexahydro azepine 4-amine. The final compound was purified by reverse phase HPLC and basified to give the free base. Further, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group was removed using 40% TFA in dichloromethane (6 ml) and purified the product using preparative HPLC. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10-2.05 (m, 16H) 2.88 (d, J=3.28 Hz, 1H) 3.01 (br. s., 2H) 3.31 (s, 3H) 3.34 (br. s., 1H) 3.94 (s, 3H) 4.06 (t, J=13.26 Hz, 3H) 4.46 (m, 1H) 7.47 (d, J=8.1 Hz, 1H) 7.50 (s, 1H) 7.91 (s, 1H) 8.21 (s, 1H) 8.23-8.30 (m, 2H). [M+H] calculated for C28H37F2N7O3, 558. found 558. as described in the General procedure for amide bond synthesis The final compound was purified by reverse phase HPLC to give the free base Further, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group was removed purified the product

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

Procedure: The title compound was synthesized from 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-N—Boc-hexahydro azepine 4-amine. The final compound was purified by reverse phase HPLC and basified to give the free base. Further, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group was removed using 40% TFA in dichloromethane (6 ml) and purified the product using preparative HPLC. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10-2.05 (m, 16H) 2.88 (d, J=3.28 Hz, 1H) 3.01 (br. s., 2H) 3.31 (s, 3H) 3.34 (br. s., 1H) 3.94 (s, 3H) 4.06 (t, J=13.26 Hz, 3H) 4.46 (m, 1H) 7.47 (d, J=8.1 Hz, 1H) 7.50 (s, 1H) 7.91 (s, 1H) 8.21 (s, 1H) 8.23-8.30 (m, 2H). [M+H] calculated for C28H37F2N7O3, 558. found 558. as described in the General procedure for amide bond synthesis The final compound was purified by reverse phase HPLC to give the free base Further, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group was removed purified the product

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

Procedure: The title compound was synthesized from 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and tert-butyl 4-aminoazepane-1-carboxylate, where Boc was removed using TFA in DCM. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41-1.65 (m, 4H) 1.65-1.83 (m, 3H) 1.83-1.99 (m, 4H) 2.07 (m., 2H) 3.16 (s, 3H) 3.32 (s, 3H) 3.93 (s, 3H) 4.07 (t, J=13.8 Hz, 3H) 4.78 (t, J=8.1 Hz, 1H) 7.41-7.54 (m, 2H) 8.14-8.29 (m, 2H) 8.31 (d, J=7.6 Hz, 1H) 8.55 (br. s., 2H). [M+H] calc'd for C27H35F2N7O3, 544. found 544. as described in the General procedure for amide bond synthesis was removed The final compound was purified by reverse phase HPLC to give the free base

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

Procedure: 4-Amino-1-tert-butyloxycarbonylazacycloheptane colourless oil; RF : 0.36 (alumina; methylene chloride/methanol=9:1)

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

Procedure: Prepared analogously to example 1.4 from 4-{4-fluoro-2-[(S)-(tetrahydro-furan-3-yl)oxy]-phenylamino}-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid and 4-amino-azepane-1-carboxylic acid tert-butyl ester.