Hydrochloric Acid → HCID 23581894, compound

HRID 1874203Notes

Reaction equation

HRID 1874203 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([C@@:11]([NH:33][C:34](=[O:46])[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[C:37]([C:42]([F:45])([F:44])[F:43])[CH:36]=2)([C:19]2[CH:24]=[C:23]([O:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])[CH:22]=[C:21]([F:32])[CH:20]=2)[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=[CH:8][C:9]=1[F:10].[CH3:47][S:48](Cl)(=[O:50])=[O:49].Cl>C(Cl)Cl>[F:41][C:38]1[CH:39]=[CH:40][C:35]([C:34]([NH:33][C@:11]([C:6]2[CH:7]=[CH:8][C:9]([F:10])=[C:4]([CH2:3][NH:2][S:48]([CH3:47])(=[O:50])=[O:49])[CH:5]=2)([C:19]2[CH:24]=[C:23]([O:25][C:26]([F:31])([F:30])[CH:27]([F:28])[F:29])[CH:22]=[C:21]([F:32])[CH:20]=2)[CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:46])=[CH:36][C:37]=1[C:42]([F:45])([F:44])[F:43]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 23581891HCID 23581891, compound

Product 1

HCID 23581894HCID 23581894, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)—N-(1-(3-(aminomethyl)-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide hydrochloride (Example 269, 30 mg, 0.04 mmol) in DCM (2 mL) at rt was added TEA (6.8 μL, 0.05 mmol) followed by methanesulfonyl chloride (3.4 μL, 0.04 mmol). The reaction mixture was stirred at rt for 1 h and then poured into 1 N HCl. The aqueous layer was extracted with CH2Cl2 and the combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by ISCO column chromatography (4 g, 0-40% EtOAc/hexane) to yield (R)-4-fluoro-N-(1-(4-fluoro-3-(methylsulfonamidomethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (Example 271) as a clear, colorless film (12 mg, 41%). 1H NMR (400 MHz, CDCl3) 7.95 (dd, J=6.57, 2.02 Hz, 1H), 7.86 (m, 1H), 7.22 (m, 7H), 7.07 (t, J=8.97 Hz, 1H), 6.93 (m, 3H), 6.71 (m, 3H), 5.88 (m, 1H), 4.55 (t, J=6.32 Hz, 1H), 4.30 (t, J=5.81 Hz, 2H), 3.97 (m, 1H), 3.83 (m, 1H), 2.81 (s, 3H).

Workup

  1. extractionThe aqueous layer was extracted with CH2Cl2
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by ISCO column chromatography (4 g, 0-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-8b0bc75ff8e24d71980a4f472d47a2cd
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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