p-Toluenesulfonic acid monohydrate → 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

HRID 1676676

反応式

HRID 1676676 の反応式
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

参加物

5

反応物 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

生成物 1

HCID 580150994-(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収率 51.8%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-c0f4ca6648a3478fb703e17b660929d8
出典データセット
uspto-grants-2011_08
特許番号
US08003785B2

関連ノート

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