Isopropanol → 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-isopropoxy-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 1676712노트

반응식

HRID 1676712 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[NH2:22][C:23]1[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[O:39][CH:40]([CH3:42])[CH3:41].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)(C)C>ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>[CH:16]1([N:7]2[CH2:8][C:9]([F:15])([F:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:22][C:23]4[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]5[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]5)=[O:28])=[CH:25][C:24]=4[O:39][CH:40]([CH3:42])[CH3:41])=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

참가 물질

7

반응물 4

HCID 3776IsopropanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-oneHCID 580149994-amino-3-isopropoxy-N-(1-methyl-piperidin-4-yl)-benzamide

생성물 1

HCID 580149734-(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-isopropoxy-N-(1-methyl-piperidin-4-yl)-benzamide수율 71.1%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 10340Sodium Carbonate용매

실험 절차

A mixture of 0.10 g (0.32 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-20), 0.11 g (0.38 mmole) of 4-amino-3-isopropoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.090 g (0.48 mmole) of p-toluenesulfonic acid monohydrate and 4 mL of isopropanol was heated in a pressure tube at 140 degrees overnight, then cooled and diluted with dichloromethane and saturated sodium carbonate. The mixture was extracted twice with dichloromethane. The combined organic layers were washed three times with sodium carbonate, three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-60:40) gave 0.13 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-isopropoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-180) as a white solid.

후처리

  1. temperaturewas heated in a pressure tube at 140 degrees overnight
  2. temperaturecooled
  3. extractionThe mixture was extracted twice with dichloromethane
  4. washThe combined organic layers were washed three times with sodium carbonate, three times with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by silica gel chromatography
  9. washeluting with dichloromethane-methanol (gradient, 100:0-60:40)

출처 및 근거

ORD 기록
ord-b9369919a30d4c64b59393e553469b3b
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003785B2

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