p-Toluenesulfonic acid monohydrate → HCID 58015099, 화합물

HRID 1676676

반응식

HRID 1676676 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH2:12][CH3:13])[C:10](=[O:14])[C:9]([F:16])([F:15])[CH2:8][N:7]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:6]=2[N:22]=1.[NH2:23][C:24]1[CH:39]=[CH:38][C:27]([C:28]([NH:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[O:29])=[CH:26][CH:25]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[CH:17]1([N:7]2[CH2:8][C:9]([F:16])([F:15])[C:10](=[O:14])[N:11]([CH2:12][CH3:13])[C:5]3[CH:4]=[N:3][C:2]([NH:23][C:24]4[CH:25]=[CH:26][C:27]([C:28]([NH:30][CH:31]5[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]5)=[O:29])=[CH:38][CH:39]=4)=[N:22][C:6]2=3)[CH2:21][CH2:20][CH2:19][CH2:18]1

참가 물질

5

반응물 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 433732804-amino-N-(1-methylpiperidin-4-yl)benzamideHCID 866375052-Chloro-9-cyclopentyl-5-ethyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

생성물 1

HCID 58015099HCID 58015099, 화합물수율 51.8%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

A mixture of 0.05 g (0.15 mmole) of 2-chloro-9-cyclopentyl-5-ethyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-138), 0.04 g (0.18 mmole) of 4-amino-N-(1-methyl-piperidin-4-yl)-benzamide, 0.04 g (0.23 mmole) of p-toluenesulfonic acid monohydrate and 4.0 mL of 2-propanol was heated at 160 degrees for 2 hours in a microwave reactor. The cooled reaction mixture was concentrated under reduced pressure. The residue was diluted with dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phases were extracted with dichloromethane, and the combined organic layers washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with methanol-dichloromethane (gradient, 0:100-25:75) to give 0.041 g of 4-(9-cyclopentyl-5-ethyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide (I-141).

후처리

  1. temperaturewas heated at 160 degrees for 2 hours in a microwave reactor
  2. customThe cooled reaction mixture
  3. concentrationwas concentrated under reduced pressure
  4. additionThe residue was diluted with dichloromethane
  5. washwashed twice with saturated aqueous sodium bicarbonate solution
  6. extractionThe aqueous phases were extracted with dichloromethane
  7. washthe combined organic layers washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel chromatography
  12. washeluting with methanol-dichloromethane (gradient, 0:100-25:75)

출처 및 근거

ORD 기록
ord-c0f4ca6648a3478fb703e17b660929d8
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003785B2

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