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 1676643ノート

反応式

HRID 1676643 の反応式
[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

参加物

8

反応物 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、化合物

生成物 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)-benzamide収率 75.8%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-fe177d840d8449a49b67a64bdfcba603
出典データセット
uspto-grants-2011_08
特許番号
US08003785B2

反応ノート

読み込み中…