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(S)-3-Amino-1-methyl-piperidine → (S)-4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-3-yl)benzamide

HRID 1880899
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HRID 1880899 반응식
[CH:1]1([N:7]2[CH2:13][C:12]([F:15])([F:14])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:6][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.[CH3:58][N:59]1[CH2:64][CH2:63][CH2:62][C@H:61]([NH2:65])[CH2:60]1>>[CH:1]1([N:7]2[CH2:13][C:12]([F:14])([F:15])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([NH:65][C@H:61]5[CH2:62][CH2:63][CH2:64][N:59]([CH3:58])[CH2:60]5)=[O:29])=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
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4

반응물 3

HCID 7446915(S)-3-Amino-1-methyl-piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252536804-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid

생성물 1

HCID 25254782(S)-4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-3-yl)benzamide

실험 절차

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 (S)-1-methylpiperidin-3-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 1.17-1.26 (m, 2 H) 1.29-1.46 (m, 3 H) 1.55-1.73 (m, 5 H) 1.75-1.90 (m, 6 H) 2.23 (br s, 3 H) 2.64-2.78 (m, 1 H) 2.79-2.95 (m, 1 H) 3.31 (s, 3 H) 3.90-4.01 (m, 1 H) 3.94 (s, 3 H) 4.07 (t, J=12.63 Hz, 2 H) 4.37-4.53 (m, 1 H) 7.47 (dd, J=8.46, 1.64 Hz, 1 H) 7.51 (d, J=1.77 Hz, 1 H) 7.91 (s, 1 H) 8.10 (d, J=7.33 Hz, 1 H) 8.21 (s, 1 H) 8.27 (d, J=8.34 Hz, 1 H). [M+H] calc'd for C28H37F2N7O3 558; found 558.

후처리

  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

출처 및 근거

ORD 기록
ord-cfb1fb997b594ac785a025685cf0d959
출처 데이터셋
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08318727B2

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