Ammonia → HCID 59458741, compound

HRID 1874255Notes

Reaction equation

HRID 1874255 reaction equation
[F:1][C:2]1[CH:41]=[CH:40][C:5]([C:6]([NH:8][C@:9]([C:31]2[CH:39]=[CH:38][C:34]([C:35](F)=[O:36])=[CH:33][CH:32]=2)([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])=[CH:4][C:3]=1[C:42]([F:45])([F:44])[F:43].[NH3:46]>C(#N)C>[C:35]([C:34]1[CH:33]=[CH:32][C:31]([C@@:9]([NH:8][C:6](=[O:7])[C:5]2[CH:40]=[CH:41][C:2]([F:1])=[C:3]([C:42]([F:43])([F:45])[F:44])[CH:4]=2)([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:26])[F:27])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:39][CH:38]=1)(=[O:36])[NH2:46]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 59458888HCID 59458888, compound

Product 1

HCID 59458741HCID 59458741, compoundYield 67.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of (R)-4-(1-(4-fluoro-3-(trifluoromethyl)benzamido)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)benzoyl fluoride (20 mg, 0.03 mmol) in acetonitrile (1 mL) was added ammonia (7 M in methanol, 20 μL, 0.14 mmol). The reaction mixture was stirred for 24 h. The reaction mixture was concentrated and the residue was purified by flash chromatography (4 g silica gel; 0-100% ethyl acetate, hexane gradient over 14 min., 18 mL/min) to provide (R)—N-(1-(4-carbamoylphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (Example 320, 13 mg, 65% yield). LCMS: RT=1.81 min [M+H] 631 (Chromolith Performance 18e 4.6×100 mm column, 50-90% methanol, water with 0.1% trifluoroacetic acid gradient over 2 min, 5 mL/min). 1H NMR (400 MHz, CDCl3) ppm 7.86 (1H, d, J=4.83 Hz), 7.77 (1H, dt, J=8.35, 2.20 Hz), 7.71 (2H, d, J=8.35 Hz), 7.14-7.25 (3H, m), 7.08 (3H, t, J=7.47 Hz), 6.85-6.90 (3H, m), 6.71 (1H, s), 6.63 (2H, d, J=7.03 Hz), 6.05 (1H, s), 5.88 (1H, tt, JHH=2.75 Hz, JHF=53 Hz), 5.70 (1H, s), 3.86 (2H, dd, J=37.4, 13.2 Hz).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by flash chromatography (4 g silica gel; 0-100% ethyl acetate, hexane gradient over 14 min., 18 mL/min)

Sources & evidence

ORD record
ord-da2aea8024d54ad1ac847a4d7e7a739e
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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