4-Amino-2,2,6,6-tetramethylpiperidine → 4-(9-cyclopentyl-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-(2,2,6,6-tetramethyl-piperidin-4-yl)-benzamide

HRID 1676610

反応式

HRID 1676610 の反応式
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.[CH3:42][C:43]1([CH3:52])[CH2:48][CH:47]([NH2:49])[CH2:46][C:45]([CH3:51])([CH3:50])[NH:44]1>CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:49][CH:47]5[CH2:48][C:43]([CH3:52])([CH3:42])[NH:44][C:45]([CH3:51])([CH3:50])[CH2:46]5)=[O:28])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

参加物

5

反応物 3

HCID 375244-Amino-2,2,6,6-tetramethylpiperidineHCID 81531DiisopropylethylamineHCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

生成物 1

HCID 445486154-(9-cyclopentyl-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-(2,2,6,6-tetramethyl-piperidin-4-yl)-benzamide収率 50.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of 0.10 g (0.22 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.12 mL (0.66 mmole) of ethyldiisopropyl amine and 0.039 g (0.25 mmole) of 2,2,6,6-tetramethyl-piperidin-4-ylamine in 2.0 mL of dimethylformamide was added 0.11 g (0.25 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate. The mixture was stirred at room temperature for 1 hour, then diluted with 10 mL of ice water. The resulting solid was collected by filtration, washed with saturated sodium carbonate and water, and dried under vacuum. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-60:40) gave 0.065 g of 4-(9-cyclopentyl-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-(2,2,6,6-tetramethyl-piperidin-4-yl)-benzamide (I-65) as a white solid.

後処理

  1. filtrationThe resulting solid was collected by filtration
  2. washwashed with saturated sodium carbonate and water
  3. customdried under vacuum
  4. customPurification by silica gel chromatography
  5. washeluting with dichloromethane-methanol (gradient, 100:0-60:40)

出典と根拠

ORDレコード
ord-34a52f707f1f45c29596c8cf98ae138e
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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