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Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (R)-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-methylpyrrolidin-3-yl)benzamide

HRID 914095
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 914095
[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=[N:49][C:44]2[CH:45]=[CH:46][CH:47]=[N:48][C:43]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.CN1CC[C@@H](N)C1>>[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]([NH:49][C@@H:44]5[CH2:45][CH2:46][N:48]([CH3:47])[CH2:43]5)=[O:29])=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

4

Edukt 3

HCID 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 acidHCID 53256048(3R)-1-Methyl-3-PyrrolidinaMine hydrochloride

Produkt 1

HCID 25253998
(R)-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-methylpyrrolidin-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 1-methyl-3-(R)-amino pyrrolidine dihydrochloride. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.15-1.90 (m, 12H) 2.18 (m, 1H) 2.26 (s, 3H) 2.32-2.56 (m, 2H) 2.60-2.68 (m, 2H) 3.34 (s, 3H) 3.95 (s, 3H) 4.07 (t, J=13.52 Hz, 2H) 4.34-4.54 (m, 2H) 7.51 (d, J=8.0 Hz, 1H), 7.54 (br. s., 1H) 7.90 (s, 1H), 8.21 (s, 1H) 8.27 (d, J=8.0 Hz, 1H) 8.40 (br. s., 1H). Melting point: 98-99° C. [M+H] calculated for C27H35F2N7O3, 544. found 544.

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-2a4069030cf0430190fec706213aab2c
Quelldatensatz
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08026234B2

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