3-Chloro-4-fluoroaniline → HCID 118222053, compound

HRID 1754298Notes

Reaction equation

HRID 1754298 reaction equation
[CH:1]1([O:4][C:5]2[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][C:6]=2[S:14]([N:17]2[CH2:23][CH:22]([OH:24])[CH2:21][O:20][CH2:19][CH2:18]2)(=[O:16])=[O:15])[CH2:3][CH2:2]1.[Cl:25][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][C:32]=1[F:33])[NH2:29].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>CN(C=O)C.O>[Cl:25][C:26]1[CH:27]=[C:28]([NH:29][C:9](=[O:11])[C:8]2[CH:12]=[CH:13][C:5]([O:4][CH:1]3[CH2:3][CH2:2]3)=[C:6]([S:14]([N:17]3[CH2:23][CH:22]([OH:24])[CH2:21][O:20][CH2:19][CH2:18]3)(=[O:15])=[O:16])[CH:7]=2)[CH:30]=[CH:31][C:32]=1[F:33]

Participants

7

Reactant 4

HCID 97083-Chloro-4-fluoroanilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118222047HCID 118222047, compound

Product 1

HCID 118222053HCID 118222053, compoundYield 40.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4-(cyclopropoxy)-3-[(6-hydroxy-1,4-oxazepan-4-yl)sulfonyl]benzoic acid (170.00 mg, 475.68 umol, 1.00 eq) and 3-chloro-4-fluoro-aniline (69.24 mg, 475.68 umol, 1.00 eq) in DMF (5.00 mL) were added HATU (180.87 mg, 475.68 umol, 1.00 eq) and DIPEA (122.95 mg, 951.36 umol, 2.00 eq). The mixture was stirred at 25° C. for 16 hr. TLC detected the reaction was complete, the mixture was poured into water, extracted with EA, the combined organic layer was dried over anhydrous Na2SO4, concentrated, the residue was purified by prep-HPLC (FA) to afford product N-(3-chloro-4-fluoro-phenyl)-4-(cyclopropoxy)-3-[(6-hydroxy-1,4-oxazepan-4-yl)sulfonyl]benzamide (94.10 mg, 194.05 umol, 40.79% yield) as white solid. 1H NMR (400 MHz, MeOD) δ 8.48 (d, J=2.01 Hz, 1H), 8.23 (dd, J=8.66, 2.13 Hz, 1H), 7.96 (dd, J=6.78, 2.51 Hz, 1H), 7.70 (d, J=8.78 Hz, 1H), 7.59-7.65 (m, 1H), 7.27 (t, J=8.91 Hz, 1H), 4.07-4.13 (m, 1H), 4.03 (t, J=6.53 Hz, 1H), 3.77-3.97 (m, 4H), 3.61-3.73 (m, 2H), 3.21-3.30 (m, 1H), 3.11 (dd, J=14.56, 7.53 Hz, 1H), 0.84-1.04 (m, 4H). LCMS: 485/487 [M+1].

Workup

  1. extractionextracted with EA
  2. dry with materialthe combined organic layer was dried over anhydrous Na2SO4
  3. concentrationconcentrated
  4. customthe residue was purified by prep-HPLC (FA)

Sources & evidence

ORD record
ord-0bdd69b737aa44359d1a1bfde82e88df
Source dataset
uspto-grants-2015_10
Patent number
US09169212B2

Reaction notes

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