Hydrochloric Acid → HCID 60152220, compound

HRID 537541Notes

Reaction equation

HRID 537541 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[CH:17]([NH:21][C:22]1[CH:23]=[N:24][C:25]([N:28]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[N:29]2)=[CH:26][CH:27]=1)[CH2:18][CH2:19][CH3:20])[C:5]([NH:7][CH2:8][CH2:9][C:10]([O:12]C)=[O:11])=[O:6].[OH-].[Li+].Cl>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[CH:17]([NH:21][C:22]1[CH:23]=[N:24][C:25]([N:28]2[CH:32]=[C:31]([C:33]([F:35])([F:34])[F:36])[CH:30]=[N:29]2)=[CH:26][CH:27]=1)[CH2:18][CH2:19][CH3:20])[C:5]([NH:7][CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[O:6]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 68156714HCID 68156714, compound

Product 1

HCID 60152220HCID 60152220, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Isomer 1 of methyl 3-(3-fluoro-4-(1-(6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-ylamino)butyl)benzamido)propanoate (180 mg, 0.36 mmol) in tetrahydrofuran (8 mL) was added 2 N aqueous lithium hydroxide (8 mL, 16 mmol). The reaction was stirred at room temperature for 1 hour. The reaction mixture was acidified to pH ˜2 with 1 N aqueous hydrochloric acid and extracted with ethyl acetate (3×5 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated to give 3-(3-fluoro-4-(1-(6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-ylamino)butyl)benzamido)propanoic acid, Isomer 1 (104 mg, 59%) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.57 (s, 1H), 7.77 (s, 1H), 7.63 (s, 1H), 7.50 (d, J=8.8 Hz, 1H), 7.43-7.46 (m, 2H), 7.34-7.38 (m, 1H), 6.93 (d, J=8.8 Hz, 1H), 4.66 (t, J=6.8 Hz, 1H), 3.48 (t, J=6.8 Hz, 2H), 2.50 (t, J=6.8 Hz, 2H), 1.65-1.82 (m, 2H), 1.17-1.49 (m, 2H), 0.89 (t, J=6.8 Hz, 3H). MS (M+1) 494.2. Chiral SFC: Chiralpak AD-3, 4.6×50 mm, 3 μm. Modifier: 0.05% DEA. Gradient: 95% CO2/5% ethanol linear to 60% CO2/40% ethanol over 3.0 minutes. Flow: 4 mL/min. Retention time: 1.74 minutes, 100% ee (Isomer 1).

Workup

  1. extractionextracted with ethyl acetate (3×5 mL)
  2. dry with materialThe combined organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-5d05499db7534bdebdd309a617af47f4
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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