Dimethylformamide → (2S,4S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-((benzylamino)methyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

HRID 1630284

反応式

HRID 1630284 の反応式
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[N:10]1([CH2:15][C:16]([N:18]2[CH2:22][C@H:21]([CH2:23][NH2:24])[CH2:20][C@H:19]2[C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)=[CH:30][CH:29]=2)=[O:26])=[O:17])[CH:14]=[N:13][CH:12]=[N:11]1.CN(C=O)C.C([O-])([O-])=O.[K+].[K+]>Cl>[N:10]1([CH2:15][C:16]([N:18]2[CH2:22][C@H:21]([CH2:23][NH:24][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:20][C@H:19]2[C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=3)=[CH:30][CH:29]=2)=[O:26])=[O:17])[CH:14]=[N:13][CH:12]=[N:11]1

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 67010106(2S,4S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-aminomethyl-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide hydrochloride salt

生成物 1

HCID 67009896(2S,4S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-((benzylamino)methyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide収率 8%

試薬・触媒・溶媒 1

HCID 313Hydrochloric Acid溶媒

実験手順

Benzyl bromide (0.067 mL, 0.56 mmol) was added to a mixture of (2S,4S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-aminomethyl-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide hydrochloride salt (0.247 g, 0.564 mmol), DMF (10 mL) and K2CO3 (0.312 g, 2.26 mmol), prepared as in Reference 12. The reaction mixture was stirred at ambient temperature for 30 minutes and then diluted with 1N hydrochloric acid (30 mL). The dilution was washed with ethyl acetate (30 mL). The aqueous layer was basified with 2N sodium hydroxide (40 mL) and extracted with methylene chloride (40 mL). The extract was washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by reverse phase HPLC to give Compound 262, (2S,4S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-((benzylamino)methyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (23 mg, 0.044 mmol, 8%), as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): 10.03 (s, 1H), 8.44 (s, 1H), 7.96 (s, 1H), 7.58 (d, J=7.6 Hz, 2H), 7.37-7.30 (m, 3H), 7.25-7.17 (m, 3H), 7.03-6.94 (m, 5H), 5.30, 5.19 (m, 2H), 4.49-4.46 (m, 2H), 3.89-3.84 (m, 1H), 3.74 (s, 2H), 2.69-2.52 (m, 2H), 2.16-1.87 (m, 2H). MS (EI) for C29H29FN6O3. found 529.3 (MH+).

後処理

  1. washThe dilution was washed with ethyl acetate (30 mL)
  2. extractionextracted with methylene chloride (40 mL)
  3. washThe extract was washed with brine (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customProduct was purified from the residue by reverse phase HPLC

出典と根拠

ORDレコード
ord-e6cabb1257334caaa5d50194a39828ea
出典データセット
uspto-grants-2014_07
特許番号
US08791102B2

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