Trifluoroacetic acid → Trifluoroacetic acid

HRID 1023176Notes

Reaction equation

HRID 1023176 reaction equation
[F:1][CH:2]([F:39])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:15]=[C:14]([CH:16]3[CH2:18][CH:17]3[C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[N:25](COCC[Si](C)(C)C)[C:24](=[O:37])[CH:23]=[CH:22]4)[O:13][N:12]=2)=[CH:6][C:5]=1[CH3:38].[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]>C(Cl)Cl>[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41].[F:39][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:15]=[C:14]([C@@H:16]3[CH2:18][C@H:17]3[C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[NH:25][C:24](=[O:37])[CH:23]=[CH:22]4)[O:13][N:12]=2)=[CH:6][C:5]=1[CH3:38]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86680422HCID 86680422, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 86680421HCID 86680421, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 6-(2-(3-((4-(difluoromethoxy)-3-methylphenyl)amino)-1,2,4-oxadiazol-5-yl)cyclopropyl)-1-((2-(trimethylsilyl)ethoxy)methyl)quinolin-2(1H)-one (60 mg, 0.108 mmol) in DCM (2 mL) was added TFA (0.042 mL, 0.541 mmol) at 0° C. and the mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with DCM and washed with sat. NaHCO3 solution. The organic layer was dried Na2SO4, and concentrated. The crude product which was purified by preparative HPLC on a Sunfire C18 column (150×19, 5μ) using a buffer of mobile phase A: 0.1% TFA/Mobile Phase-B: ACN to give trans-6-(2-(3-((4-(difluoromethoxy)-3-methylphenyl)amino)-1,2,4-oxadiazol-5-yl)cyclopropyl)quinolin-2(1H)-one as an off white solid (12 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.70-1.83 (m, 2H) 2.22 (s, 3H) 2.56-2.64 (m, 1H) 2.72-2.78 (m, 1H) 6.51 (dd, J=9.54, 2.01 Hz, 1H) 6.84-7.15 (m, 2H) 7.24 (d, J=3.01 Hz, 1H) 7.29-7.35 (m, 2H) 7.43 (dd, J=8.66, 1.88 Hz, 1H) 7.58 (d, J=1.76 Hz, 1H) 7.84 (d, J=9.54 Hz, 1H) 9.83 (s, 1H) 11.72 (s, 1H). LCMS, RT 2.23 min; LCMS (ES-API), m/z 425.2.

Workup

  1. washwashed with sat. NaHCO3 solution
  2. concentrationconcentrated
  3. customThe crude product which was purified by preparative HPLC on a Sunfire C18 column (150×19, 5μ)

Sources & evidence

ORD record
ord-7fca2f4b55d547aebbb0a40a26e7844e
Source dataset
uspto-grants-2014_05
Patent number
US08722670B2

Reaction notes

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