Diisopropylethylamine → 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-methoxy-N-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-benzamide

HRID 1676643노트

반응식

HRID 1676643 반응식
[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[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)C(C)C)C.[N:66]1([C:73]2[CH:78]=[CH:77][CH:76]=[CH:75][N:74]=2)[CH2:71][CH2:70][CH:69]([NH2:72])[CH2:68][CH2:67]1>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[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:72][CH:69]5[CH2:70][CH2:71][N:66]([C:73]6[CH:78]=[CH:77][CH:76]=[CH:75][N:74]=6)[CH2:67][CH2:68]5)=[O:28])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 101979341-(Pyridin-2-yl)piperidin-4-amineHCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acidHCID 178484293HCID 178484293, 화합물

생성물 1

HCID 580150224-(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-methoxy-N-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-benzamide수율 75.8%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 516892Sodium Bicarbonate용매

실험 절차

A mixture of 0.045 g (0.1 mmole) of 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-methoxybenzoic acid (I-22), 0.042 g (0.110 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.052 ml (0.300 mmole) of ethyldiisopropyl amine and 1.0 mL of dimethylformamide was stirred for 5 minutes and then 0.021 g (0.12 mmole) 3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-ylamine was added. The mixture was stirred for 3 hours, then diluted with 10 mL of water plus 2 mL of saturated aqueous sodium bicarbonate and then extracted 3 times with 10 mL of ethyl acetate. The combined extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase silica gel chromatography, eluting with water-acetonitrile (gradient, 0:100-80:20) to give 0.046 g of 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-methoxy-N-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-benzamide (I-108) as a white solid.

후처리

  1. stirringThe mixture was stirred for 3 hours
  2. extractionextracted 3 times with 10 mL of ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by reverse phase silica gel chromatography
  8. washeluting with water-acetonitrile (gradient, 0:100-80:20)

출처 및 근거

ORD 기록
ord-fe177d840d8449a49b67a64bdfcba603
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003785B2

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