Lithium Hydroxide → 3-(3-((2-(4-((3-(Trifluoromethyl)benzyl) carbamoyl)pyridin-2-yl)phenyl)-carbamoyl)benzylthio)propanoic acid

HRID 625313Notes

Reaction equation

HRID 625313 reaction equation
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[CH2:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[NH:22][C:23]([C:25]2[CH:26]=[C:27]([CH:36]=[CH:37][CH:38]=2)[CH2:28][S:29][CH2:30][CH2:31][C:32]([O:34]C)=[O:33])=[O:24])[CH:11]=1)=[O:9].[Li+].[OH-]>O1CCCC1.O>[F:43][C:2]([F:1])([F:42])[C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[CH2:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[NH:22][C:23]([C:25]2[CH:26]=[C:27]([CH:36]=[CH:37][CH:38]=2)[CH2:28][S:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[O:24])[CH:11]=1)=[O:9]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 66586726Methyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzylthio)propanoate

Product 1

HCID 665880453-(3-((2-(4-((3-(Trifluoromethyl)benzyl) carbamoyl)pyridin-2-yl)phenyl)-carbamoyl)benzylthio)propanoic acidYield 20.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Into a 100-mL 3-necked round bottom flask, was placed a solution of methyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzylthio)propanoate (250 mg, 0.41 mmol, 1.00 equiv) in tetrahydrofuran (8 mL), and a solution of LiOH (98 mg, 4.08 mmol, 10.00 equiv) in water (2 mL). The resulting solution was stirred for 2 h at room temperature. The reaction progress was monitored by LCMS. The reaction was then quenched with 50 mL of water. The solution was adjusted to pH 3 with hydrochloric acid. The resulting solution was extracted with of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The crude product (120 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained 50 mg (20%) of a white solid. 1H-NMR (400 MHz, DMSO-d6, ppm): δ 13.02 (s, 1H), 9.60-9.56 (t, 1H), 9.01-8.99 (d, 1H), 8.60-8.57 (d, 1H), 8.42 (s, 1H), 8.05-8.03 (d, 1H), 7.93-7.82 (m, 3H), 7.72-7.51 (m, 7H), 7.35-7.30 (t, 1H), 4.65-4.63 (d, 2H), 3.91 (s, 2H), 2.64-2.59 (m, 3H). MS (ES, m/z): 594 [M+H]+.

Workup

  1. customInto a 100-mL 3-necked round bottom flask, was placed
  2. customThe reaction was then quenched with 50 mL of water
  3. extractionThe resulting solution was extracted with of ethyl acetate
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe solids were filtered out
  6. concentrationThe resulting mixture was concentrated under vacuum
  7. customThe crude product (120 mg) was purified by reverse phase HPLC
  8. washeluting with a water/CH3CN gradient
  9. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-7a3e6c09c063418889778863f8b27050
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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