Sodium Carbonate → 4-(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-methyl-piperidin-4-yl)-benzamide

HRID 1676841노트

반응식

HRID 1676841 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][NH:7][C:6]=2[N:16]=1.[NH2:17][C:18]1[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)=[O:23])=[CH:20][C:19]=1[O:34][CH3:35].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C(O)(C)C>[F:14][C:9]1([F:15])[CH2:8][NH:7][C:6]2[N:16]=[C:2]([NH:17][C:18]3[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH:25]4[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]4)=[O:23])=[CH:20][C:19]=3[O:34][CH3:35])[N:3]=[CH:4][C:5]=2[N:11]([CH3:12])[C:10]1=[O:13]

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 866375242-Chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-6H-pyrimido[4,5-b][1,4]diazepin-6-one

생성물 1

HCID 580150544-(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-methyl-piperidin-4-yl)-benzamide수율 33.5%

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 0.08 g (0.32 mmole) of 2-chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-292), 0.093 g (0.35 mmole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.092 g (0.48 mmole) of p-toluenesulfonic acid monohydrate and 4 mL of isopropanol was heated in pressure tube at 120 degrees overnight. After cooling, dichloromethane and saturated sodium carbonate were added. The mixture was extracted twice with dichloromethane. The combined organic layers were washed three times with sodium carbonate, times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by C18 reverse phase silica gel chromatography, eluting with acetonitrile-water (gradient, 10:90-100:0) to gave 0.051 g of give 4-(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-methyl-piperidin-4-yl)-benzamide (I-303) as a white solid.

후처리

  1. temperaturewas heated in pressure tube at 120 degrees overnight
  2. temperatureAfter cooling
  3. extractionThe mixture was extracted twice with dichloromethane
  4. washThe combined organic layers were washed three times with sodium carbonate, times with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by C18 reverse phase silica gel chromatography
  9. washeluting with acetonitrile-water (gradient, 10:90-100:0)

출처 및 근거

ORD 기록
ord-2e92283cd5db4d59920733ccb95d768d
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003785B2

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