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 1499515Notes

Reaction equation

HRID 1499515 reaction equation
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]

Participants

6

Reactant 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

Product 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-carboxamideYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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%).

Workup

  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.)

Sources & evidence

ORD record
ord-997d97c75a5c42b9b9acdc0bfcd9087f
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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