Water → HCID 68157402, compound

HRID 1520937Notes

Reaction equation

HRID 1520937 reaction equation
[F:1][C:2]1([F:37])[CH2:5][CH:4]([CH:6]([NH:21][C:22]2[CH:23]=[N:24][C:25]([N:28]3[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[N:30]=[CH:29]3)=[CH:26][CH:27]=2)[C:7]2[CH:20]=[CH:19][C:10]([C:11]([NH:13][CH2:14][CH2:15][C:16]([O-:18])=[O:17])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1.O.O1CCCC1.O.[OH-].[Li+]>CO>[F:37][C:2]1([F:1])[CH2:5][CH:4]([CH:6]([NH:21][C:22]2[CH:23]=[N:24][C:25]([N:28]3[CH:32]=[C:31]([C:33]([F:34])([F:35])[F:36])[N:30]=[CH:29]3)=[CH:26][CH:27]=2)[C:7]2[CH:20]=[CH:19][C:10]([C:11]([NH:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 86669090HCID 86669090, compound

Product 1

HCID 68157402HCID 68157402, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a flask containing 3-(4-((3,3-difluorocyclobutyl)(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridin-3-ylamino)methyl)benzamido)propanoate (7.00 mg, 0.0100 mmol) was added water (0.0650 mL), tetrahydrofuran (0.0650 mL), and methanol (0.0650 mL). Lithium hydroxide monohydrate (27.3 mg, 0.650 mmol) was then added. The suspension was stirred at room temperature for 2 hours. The reaction was quenched with 1 N hydrochloric acid to pH 3 and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give (+/−)-3-(4-((3,3-difluorocyclobutyl)(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridin-3-ylamino)methyl)benzamido)propanoic acid (4.5 mg, 70%) of a glass-like material. 1H NMR (400 MHz, CDCl3) δ 8.36-8.34 (m, 1H), 8.16-8.12 (m, 1H), 7.86 (d, J=2.9 Hz, 1H), 7.84-7.77 (m, 2H), 7.58-7.51 (m, 2H), 7.39 (dd, J=8.8, 0.6 Hz, 1H), 7.10 (dd, J=8.8, 2.9 Hz, 1H), 4.48 (d, J=8.8 Hz, 1H), 3.63 (t, J=6.9 Hz, 2H), 2.94-2.73 (m, 1H), 2.64 (t, J=6.9 Hz, 2H), 2.61-2.49 (m, 2H), 2.49-2.33 (m, 2H). MS (M+1): 524.3.

Workup

  1. customThe reaction was quenched with 1 N hydrochloric acid to pH 3
  2. extractionextracted three times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-6510476725d04cf484510618ca7d40db
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

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