Sodium Carbonate → 4-[9-cyclopentyl-7,7-difluoro-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 1676684노트

반응식

HRID 1676684 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:10](=[O:17])[C:9]([F:19])([F:18])[CH2:8][N:7]([CH:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[C:6]=2[N:25]=1.[NH2:26][C:27]1[CH:42]=[CH:41][C:30]([C:31]([NH:33][CH:34]2[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]2)=[O:32])=[CH:29][C:28]=1[O:43][CH3:44].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C(O)(C)C>[CH:20]1([N:7]2[CH2:8][C:9]([F:19])([F:18])[C:10](=[O:17])[N:11]([CH2:12][C:13]([F:14])([F:15])[F:16])[C:5]3[CH:4]=[N:3][C:2]([NH:26][C:27]4[CH:42]=[CH:41][C:30]([C:31]([NH:33][CH:34]5[CH2:35][CH2:36][N:37]([CH3:40])[CH2:38][CH2:39]5)=[O:32])=[CH:29][C:28]=4[O:43][CH3:44])=[N:25][C:6]2=3)[CH2:24][CH2:23][CH2:22][CH2:21]1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 866375072-Chloro-9-cyclopentyl-7,7-difluoro-5-(2,2,2-trifluoro-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

생성물 1

HCID 580151024-[9-cyclopentyl-7,7-difluoro-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide수율 47.2%

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 0.10 g (0.26 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-(2,2,2-trifluoro-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-150), 0.072 g (0.27 mmole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.074 g (0.39 mmole) of p-toluenesulfonic acid monohydrate and 4 mL of isopropanol was heated in a pressure tube at 140 degrees overnight. After cooling, dichloromethane and saturated sodium carbonate were added. The mixture was extracted with dichloromethane twice. 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 (100:0-70:30) gave 0.075 g of 4-[9-cyclopentyl-7,7-difluoro-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-150) as a white solid.

후처리

  1. temperaturewas heated in a pressure tube at 140 degrees overnight
  2. temperatureAfter cooling
  3. extractionThe mixture was extracted with dichloromethane twice
  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 (100:0-70:30)

출처 및 근거

ORD 기록
ord-d66eaa55d98945eb9abe4018ab0e1685
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003785B2

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