Potassium Hydroxide → (S)-pyrrolidine-2-carboxylic acid [4-methoxy-3-(3-pyrazin-2-yl-ureido)-phenyl]-amide

HRID 1821729Notes

Reaction equation

HRID 1821729 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C@@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2C(=O)C(F)(F)F)=[O:11])=[CH:5][C:4]=1[NH:23][C:24]([NH:26][C:27]1[CH:32]=[N:31][CH:30]=[CH:29][N:28]=1)=[O:25].[OH-].[K+]>CO.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C@@H:12]2[CH2:16][CH2:15][CH2:14][NH:13]2)=[O:11])=[CH:5][C:4]=1[NH:23][C:24]([NH:26][C:27]1[CH:32]=[N:31][CH:30]=[CH:29][N:28]=1)=[O:25]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 86587622(S)-1-(2,2,2-trifluoroethanoyl)-pyrrolidine-2-carboxylic acid [4-methoxy-3-(3-pyrazin-2-yl-ureido)-phenyl]-amide2×

Product 1

HCID 67256377(S)-pyrrolidine-2-carboxylic acid [4-methoxy-3-(3-pyrazin-2-yl-ureido)-phenyl]-amide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

A suspension of (S)-1-(2,2,2-trifluoro-ethanoyl)-pyrrolidine-2-carboxylic acid [4-methoxy-3-(3-pyrazin-2-yl-ureido)-phenyl]-amide (Compound 36, Example 6) (22 mg, 0.05 mmol) in a mixture of methanol (MeOH, 5 mL) and water (about 0.25 mL) was treated with KOH (100 mg, large excess). Within 10 minutes, all ingredients were in solution. The reaction mixture was treated with water (20 mL) and extracted with ethyl acetate (2×20 mL). The organic layers were combined and washed with water (10 mL) and brine (10 mL), dried with sodium sulfate, and concentrated to a tan solid (13 mg, 75%). 1H NMR (300 MHz, d6-DMSO) δ: 10.13 (s, 1H), 10.03 (s, 1H), 9.85 (s, 1H), 8.90 (s, 1H), 8.38-8.28 (m, 2H), 8.25 (d, J=2.6 Hz, 1H), 7.41 (dd, J=8.8, 2.6 Hz), 6.98 (d, J=8.8 Hz, 1H), 3.88 (s, 3H, 3.69 (dd, J=8.7, 5.6 Hz, 1H), 2.94-2.87 (m, 2H), 2.10-1.97 (m, 1H), 1.81-1.60 (m, 3H). LRMS (ESI, positive) m/e 357.1 (M+1).

Workup

  1. extractionextracted with ethyl acetate (2×20 mL)
  2. washwashed with water (10 mL) and brine (10 mL)
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrated to a tan solid (13 mg, 75%)

Sources & evidence

ORD record
ord-855d31827d7a43738344db3851c9e152
Source dataset
uspto-grants-2009_10
Patent number
US07608618B2

Reaction notes

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