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-(tetrahydro-pyran-4-yl)-benzamide

HRID 1676677

反応式

HRID 1676677 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:38]=[CH:37][C:27]([C:28]([NH:30][CH:31]2[CH2:36][CH2:35][O:34][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][O:34][CH2:33][CH2:32]5)=[O:29])=[CH:37][CH:38]=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 436095624-amino-N-(oxan-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 580150054-(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-(tetrahydro-pyran-4-yl)-benzamide収率 46.6%

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-(tetrahydro-pyran-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 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 hexanes-ethyl acetate (30:70), followed by recrystallization from ethyl acetate-hexanes-methanol to give 0.036 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-(tetrahydro-pyran-4-yl)-benzamide (I-143).

後処理

  1. temperaturewas heated at 160 degrees for 2 hours in a microwave reactor
  2. concentrationThe cooled mixture was concentrated under reduced pressure
  3. additionThe residue was diluted with dichloromethane
  4. washwashed twice with saturated aqueous sodium bicarbonate solution
  5. extractionThe aqueous phases were extracted with dichloromethane
  6. washthe combined organic layers washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with hexanes-ethyl acetate (30:70)
  12. customfollowed by recrystallization from ethyl acetate-hexanes-methanol

出典と根拠

ORDレコード
ord-c931d09e576748e292e61096d24ddd1f
出典データセット
uspto-grants-2011_08
特許番号
US08003785B2

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