Trifluoroacetic acid → 3-{1-[4-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-3-(1-piperidin-4-ylmethyl-1H-benzimidazol-2-yl)-butyryl]-piperidin-4-yl}-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one

HRID 494754ノート

反応式

HRID 494754 の反応式
[NH2:1][C:2]1[C:32]([C:33]([F:36])([F:35])[F:34])=[CH:31][C:5]([CH2:6][CH:7]([CH2:10][C:11](=[O:30])[N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:24][CH2:23][C:22]4[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=4[NH:20][C:19]3=[O:29])[CH2:14][CH2:13]2)[CH:8]=O)=[CH:4][C:3]=1[Cl:37].[NH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[NH:45][CH2:46][CH:47]1[CH2:52][CH2:51][N:50](C(OC(C)(C)C)=O)[CH2:49][CH2:48]1.C(O)(C(F)(F)F)=O>CN(C=O)C.ClCCl>[NH2:1][C:2]1[C:32]([C:33]([F:34])([F:36])[F:35])=[CH:31][C:5]([CH2:6][CH:7]([C:8]2[N:45]([CH2:46][CH:47]3[CH2:48][CH2:49][NH:50][CH2:51][CH2:52]3)[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=3[N:38]=2)[CH2:10][C:11]([N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[CH2:24][CH2:23][C:22]4[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=4[NH:20][C:19]3=[O:29])[CH2:16][CH2:17]2)=[O:30])=[CH:4][C:3]=1[Cl:37]

参加物

6

反応物 3

HCID 6422Trifluoroacetic acidHCID 221845352-(4-Amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyraldehyde2 回HCID 53255822tert-Butyl 4-(((2-aminophenyl)amino)methyl)piperidine-1-carboxylate2 回

生成物 1

HCID 102404223-{1-[4-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-3-(1-piperidin-4-ylmethyl-1H-benzimidazol-2-yl)-butyryl]-piperidin-4-yl}-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 537 mg (1.000 mmol) 2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyraldehyde (Intermediate product 36) in 10 mL DMF was added tert. butyl 4-[(2-amino-phenylamino)-methyl]-piperidin-1-carboxylate (Intermediate product 34) and the mixture was stirred for 16 hours in an atmosphere of air at RT. The reaction mixture was poured onto ice water, the precipitate formed was filtered off, washed with water and dried i. vac. (Yield: 790 mg, 96% of theory). 1 mL of TFA was added to a solution of 580 mg (0.705 mmol) of the crude product in 10 mL dichloromethane and the mixture was stirred for 16 hours at RT. The reaction mixture was diluted with dichloromethane, the org. phase was washed with sat. aqueous sodium bicarbonate solution, dried over sodium sulphate and evaporated i. vac. The residue was dissolved in 3.5 mL DMF and purified by HPLC-MS (Zorbax Bonus C18 amide-phase 5 μm, gradient 0.15% formic acidin water/acetonitrile 10/90→90/10 v/v) and then lyophilised.

後処理

  1. additionThe reaction mixture was poured onto ice water
  2. customthe precipitate formed
  3. filtrationwas filtered off
  4. washwashed with water
  5. customdried i
  6. stirringthe mixture was stirred for 16 hours at RT
  7. washphase was washed with sat. aqueous sodium bicarbonate solution
  8. dry with materialdried over sodium sulphate
  9. customevaporated i
  10. dissolutionThe residue was dissolved in 3.5 mL DMF
  11. custompurified by HPLC-MS (Zorbax Bonus C18 amide-phase 5 μm, gradient 0.15% formic acidin water/acetonitrile 10/90→90/10 v/v)

出典と根拠

ORDレコード
ord-69b29c714d8d48c68778a852c284ddb7
出典データセット
uspto-grants-2009_05
特許番号
US07538115B2

反応ノート

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