Trifluoroacetic acid → HCID 77845071, compound

HRID 1484184Notes

Reaction equation

HRID 1484184 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[CH:15]=[C:14]([C:16]([F:22])([F:21])[C:17]([F:20])([F:19])[F:18])[CH:13]=[CH:12][C:8]=2[C:9](O)=[O:10])=[C:4]([O:25][CH3:26])[CH:3]=1.[NH2:27][C:28]1[CH:40]=[CH:39][C:31]([C:32]([O:34]C(C)(C)C)=[O:33])=[CH:30][CH:29]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.C(O)(C(F)(F)F)=O>CN(C=O)C.CO.O>[F:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[CH:15]=[C:14]([C:16]([F:21])([F:22])[C:17]([F:20])([F:19])[F:18])[CH:13]=[CH:12][C:8]=2[C:9]([NH:27][C:28]2[CH:29]=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:39][CH:40]=2)=[O:10])=[C:4]([O:25][CH3:26])[CH:3]=1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 233272Benzoic acid, 4-amino-, 1,1-dimethylethyl esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90314761HCID 90314761, compound

Product 1

HCID 77845071HCID 77845071, compoundYield 10.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-(4-fluoro-2-methoxy-phenoxy)-4-(1,1,2,2,2-pentafluoroethyl)benzoic acid (152.1 mg, 0.10 mmol), tert-butyl 4-aminobenzoate (21.26 mg, 0.11 mmol) and HATU (41.83 mg, 0.11 mmol) in DMF (0.5 mL) was added N-methylmorpholine (24.18 μL, 0.22 mmol) and the mixture was stirred at 25° C. for 16 hours. The mixture was poured into water and extracted with ethyl acetate (3×). The organics were combined, evaporated and taken up in dichloromethane (0.25 mL). TFA (0.25 mL, 3.245 mmol) was added and the reaction mixture was stirred at 25° C. for 1 h. The mixture was diluted with MeOH, filtered and purified by reverse phase HPLC using a gradient of acetonitrile in water (1-99%) containing HCl as a modifier to give 4-[[2-(4-fluoro-2-methoxy-phenoxy)-4-(1,1,2,2,2-pentafluoroethyl)benzoyl]amino]benzoic acid (27) (5.16 mg, 10%) as a white solid. ESI-MS m/z calc. 499.07. found 500.3 (M+1)+; Retention time: 1.82 minutes (3 minutes run). 1H NMR (400 MHz, DMSO) δ 12.80 (s, 1H), 10.84 (s, 1H), 7.94 (d, J=8.6 Hz, 2H), 7.87 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.8 Hz, 2H), 7.52 (d, J=7.9 Hz, 1H), 7.40-7.27 (m, 1H), 7.16 (dd, J=10.6, 2.8 Hz, 1H), 6.98-6.82 (m, 1H), 6.77 (s, 1H), 3.73 (s, 3H) ppm.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. customevaporated
  3. stirringthe reaction mixture was stirred at 25° C. for 1 h
  4. filtrationfiltered
  5. custompurified by reverse phase HPLC
  6. additioncontaining HCl as a modifier

Sources & evidence

ORD record
ord-16df7718762c430f839c73558c5134a1
Source dataset
uspto-grants-2016_08
Patent number
US09421196B2

Reaction notes

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