4-Amino-1-methylpiperidine → 3-Chloro-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 1880849Notes

Reaction equation

HRID 1880849 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][C:23]=4[Cl:31])=[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.[CH3:56][N:57]1[CH2:62][CH2:61][CH:60]([NH2:63])[CH2:59][CH2:58]1>>[Cl:31][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][C:22]=1[NH:21][C:19]1[N:18]=[CH:17][C:8]2[N:9]([CH3:16])[C:10](=[O:15])[C:11]([F:13])([F:14])[CH2:12][N:6]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[C:7]=2[N:20]=1)[C:26]([NH:63][CH:60]1[CH2:61][CH2:62][N:57]([CH3:56])[CH2:58][CH2:59]1)=[O:28]

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 671178444-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-chlorobenzoic acid

Product 1

HCID 252535263-Chloro-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

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)-3-chlorobenzoic 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 1.44-1.77 (m, 15 H) 2.23 (s, 3 H) 2.84 (m, 2 H) 3.96-4.07 (t, J=12 Hz, 2 H) 4.66 (m, 1 H) 7.80 (dd, J=8.5, 1.9 Hz, 1 H) 8.00 (d, J=1.8 Hz, 1 H) 8.08 (d, J=8.6 Hz, 1 H) 8.19-8.33 (m, 2 H) 8.58 (s, 1 H). [M+H] calc'd for C26H32ClF2N7O2, 548; found 548.

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 1.44-1.77 (m, 15 H) 2.23 (s, 3 H) 2.84 (m, 2 H) 3.96-4.07 (t, J=12 Hz, 2 H) 4.66 (m, 1 H) 7.80 (dd, J=8.5, 1.9 Hz, 1 H) 8.00 (d, J=1.8 Hz, 1 H) 8.08 (d, J=8.6 Hz, 1 H) 8.19-8.33 (m, 2 H) 8.58 (s, 1 H)

Sources & evidence

ORD record
ord-0a857a0361e040c799661935c828fba9
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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