4-Chloro-3-(trifluoromethyl)aniline → HCID 58674357, compound

HRID 1994136Notes

Reaction equation

HRID 1994136 reaction equation
[NH2:1][C:2]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]([OH:21])=O)=[CH:13][CH:12]=2)[CH:7]=[CH:6][N:5]=1)=[O:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Cl:55][C:56]1[CH:62]=[CH:61][C:59]([NH2:60])=[CH:58][C:57]=1[C:63]([F:66])([F:65])[F:64]>CN(C=O)C.CCOC(C)=O>[Cl:55][C:56]1[CH:62]=[CH:61][C:59]([NH:60][C:19](=[O:21])[CH2:18][CH2:17][C:14]2[CH:13]=[CH:12][C:11]([O:10][C:8]3[CH:7]=[CH:6][N:5]=[C:4]([C:2]([NH2:1])=[O:3])[CH:9]=3)=[CH:16][CH:15]=2)=[CH:58][C:57]=1[C:63]([F:64])([F:65])[F:66]

Participants

7

Reactant 4

HCID 675744-Chloro-3-(trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58674472HCID 58674472, compound

Product 1

HCID 58674357HCID 58674357, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(4-{[2-(aminocarbonyl)pyridin-4-yl]oxy}phenyl)-propanoic acid (200 mg, 0.70 mmol), HATU (319 mg, 0.84 mmol), DIPEA (0.24 mL, 1.4 mmol), and 4-chloro-3-(trifluoromethyl)aniline (136 mg, 0.70 mmol) in DMF (5 mL) was stirred overnight at rt. EtOAc was added to the reaction and the mixture was washed with 1N HCl, 1N NaOH, and brine, dried over Na2SO4 and concentrated. Purification by column chromatography (SiO2, 20-100% EtOAc in hexane) followed by recrystallization in EtOAc/hexane provided A-3 (37 mg, 11%). 1H NMR (300 MHz, d6-DMSO) δ: 10.36 (s, 1H), 8.48 (d, J=5.7 Hz, 1H), 8.18 (d, J=2.5 Hz, 1H), 8.09 (bs, 1H), 7.81 (dd, J1=2.5 Hz, J2=8.8, 1H), 7.7 (bs, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.35-7.40 (m, 3H), 7.12-7.16 (m, 3H), 2.97 (t, J=7.3 Hz, 2H), and 2.70 (t, J=7.8 Hz, 2H).

Workup

  1. washthe mixture was washed with 1N HCl, 1N NaOH, and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customPurification by column chromatography (SiO2, 20-100% EtOAc in hexane)
  5. customfollowed by recrystallization in EtOAc/hexane provided A-3 (37 mg, 11%)

Sources & evidence

ORD record
ord-172d1f8d6ff341d3bd76bca10969d1a4
Source dataset
uspto-grants-2010_01
Patent number
US07652041B2

Reaction notes

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