Methanol → 5-Amino-N-{4-[(3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide

HRID 1499515ノート

反応式

HRID 1499515 の反応式
C([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:32][C:33]([C:35]3[N:36]=[C:37]([C:48]4[C:53]([F:54])=[CH:52][CH:51]=[CH:50][C:49]=4[F:55])[S:38][C:39]=3[NH:40]C(OC(C)(C)C)=O)=[O:34])[C:13]([N:14]3[CH2:19][C@H:18]([C:20]([F:23])([F:22])[F:21])[CH2:17][C@H:16]([NH:24]C(OC(C)(C)C)=O)[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=O)C.[OH-].[Na+].O.CO>C1COCC1>[NH2:40][C:39]1[S:38][C:37]([C:48]2[C:49]([F:55])=[CH:50][CH:51]=[CH:52][C:53]=2[F:54])=[N:36][C:35]=1[C:33]([NH:32][C:12]1[C:13]([N:14]2[CH2:19][C@H:18]([C:20]([F:22])([F:23])[F:21])[CH2:17][C@H:16]([NH2:24])[CH2:15]2)=[C:8]2[CH2:7][CH2:6][CH:5]([OH:4])[C:9]2=[N:10][CH:11]=1)=[O:34]

参加物

6

反応物 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium HydroxideHCID 867267453-({[5-[(tert-Butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-4-[(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-(trifluoromethyl)piperidin-1-yl]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

生成物 1

HCID 867267465-Amino-N-{4-[(3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide収率 24%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 3-({[5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-4-[(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-(trifluoromethyl)piperidin-1-yl]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (110.3 mg, 0.1384 mmol) in THF (1.0 mL) was added a 1.0 M NaOH solution in water (1.00 mL, 1.00 mmol) followed by MeOH (2.0 mL). The reaction mixture was stirred at room temperature for 1 h, and then concentrated under reduced pressure. To the resulting residue was added DCM (2.0 mL), followed by TFA (2.0 mL). The mixture was stirred at room temperature for 30 min., and then concentrated under reduced pressure. The resulting residue was purified using RP-HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.) to afford both diastereoisomers of the title compound as white solids (9.3 mg for each, total yield 24%).

後処理

  1. concentrationconcentrated under reduced pressure
  2. additionTo the resulting residue was added DCM (2.0 mL)
  3. stirringThe mixture was stirred at room temperature for 30 min.
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified
  6. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.)

出典と根拠

ORDレコード
ord-997d97c75a5c42b9b9acdc0bfcd9087f
出典データセット
uspto-grants-2015_12
特許番号
US09200004B2

反応ノート

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