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

HRID 523637Notes

Reaction equation

HRID 523637 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-bb03d5ce650944e6b26f9fb98606312d
Source dataset
uspto-grants-2016_05
Patent number
US09339510B2

Reaction notes

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