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 1880848Notes

Reaction equation

HRID 1880848 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, 6 H) 1.72 (m, 4 H) 1.92-1.99 (m, 5 H) 2.15 (s, 3 H) 2.76 (d, J=11.4 Hz, 2 H) 3.71 (m, 1 H) 4.04 (t, J=14.2 Hz, 2 H) 4.78 (t, J=7.8 Hz, 1 H) 7.77 (s, 4 H) 8.03 (d, J=7.6 Hz, 1 H) 8.27 (s, 1 H) 9.67 (s, 1 H). 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, 6 H) 1.72 (m, 4 H) 1.92-1.99 (m, 5 H) 2.15 (s, 3 H) 2.76 (d, J=11.4 Hz, 2 H) 3.71 (m, 1 H) 4.04 (t, J=14.2 Hz, 2 H) 4.78 (t, J=7.8 Hz, 1 H) 7.77 (s, 4 H) 8.03 (d, J=7.6 Hz, 1 H) 8.27 (s, 1 H) 9.67 (s, 1 H)

Sources & evidence

ORD record
ord-35781a569b3c4ca5bccc9b0c22252888
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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