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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 914128
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 914128
[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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Komponenten

4

Edukt 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

Produkt 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

Versuchsvorschrift

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

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-aa41a6a4dbe64438a549f969a21ddc12
Quelldatensatz
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08026234B2

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