4-Amino-1-methylpiperidine → 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide

HRID 914077Notes

Reaction equation

HRID 914077 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][CH:23]=4)=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:55][N:56]1[CH2:61][CH2:60][CH:59]([NH2:62])[CH2:58][CH2:57]1>>[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:62][CH:59]5[CH2:60][CH2:61][N:56]([CH3:55])[CH2:57][CH2:58]5)=[O:28])=[CH:24][CH:23]=4)=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 445474964-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acid

Product 1

HCID 252535254-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methylpiperidin-4-yl)benzamide

Procedure

The title compound was synthesized from 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-methylpiperidin-4-amine. The final compound was purified by reverse phase HPLC and basified to give the free base 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.66 (m, 6H) 1.72 (m, 4H) 1.92-1.99 (m, 5H) 2.15 (s, 3H) 2.76 (d, J=11.4 Hz, 2H) 3.71 (m, 1H) 4.04 (t, J=14.2 Hz, 2H) 4.78 (t, J=7.8 Hz, 1H) 7.77 (s, 4H) 8.03 (d, J=7.6 Hz, 1H) 8.27 (s, 1H) 9.67 (s, 1H). Melting point: 234-2350C. [M+H] calc'd for C26H33F2N7O2, 514. found 514.

Workup

  1. customas described in the General procedure for amide bond synthesis
  2. customThe final compound was purified by reverse phase HPLC
  3. customto give the free base 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.66 (m, 6H) 1.72 (m, 4H) 1.92-1.99 (m, 5H) 2.15 (s, 3H) 2.76 (d, J=11.4 Hz, 2H) 3.71 (m, 1H) 4.04 (t, J=14.2 Hz, 2H) 4.78 (t, J=7.8 Hz, 1H) 7.77 (s, 4H) 8.03 (d, J=7.6 Hz, 1H) 8.27 (s, 1H) 9.67 (s, 1H)

Sources & evidence

ORD record
ord-99e77cc0345a4351820211c7e2e89d7e
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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