Ammonia → HCID 59458657, compound

HRID 238756Notes

Reaction equation

HRID 238756 reaction equation
[F:1][C:2]([F:40])([CH2:6][NH:7][C:8]([NH:10][C@@:11]([C:26]1[CH:31]=[C:30]([O:32][C:33]([F:38])([F:37])[CH:34]([F:36])[F:35])[CH:29]=[C:28]([F:39])[CH:27]=1)([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:9])[C:3]([OH:5])=O.C(Cl)(=O)OCC.CC[N:49](CC)CC.N>C(Cl)Cl>[F:1][C:2]([F:40])([CH2:6][NH:7][C:8]([NH:10][C@@:11]([C:26]1[CH:31]=[C:30]([O:32][C:33]([F:37])([F:38])[CH:34]([F:35])[F:36])[CH:29]=[C:28]([F:39])[CH:27]=1)([C:19]1[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=1)[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:9])[C:3]([NH2:49])=[O:5]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 59459066HCID 59459066, compound

Product 1

HCID 59458657HCID 59458657, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2,2-difluoro-3-(3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)ureido)propanoic acid (60 mg, 0.1 mmol) in CH2Cl2 (1 mL) at 0° C. was added ethyl carbonochloridate (10 uL, 0.1 mmol), followed by NEt3 (0.021 mL, 0.15 mmol) and NH3*H2O (0.1 mL, 2.6 mmol). The reaction mixture was stirred at rt for 30 min, then concentrated under reduced pressure and purified by prep HPLC (Phenomenex AXIA Luna 75×30 mm, 5μ column eluting with 10-90% ACN/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm) to yield (R)-2,2-difluoro-3-(3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)ureido)propanamide as a white solid (12 mg, 21% yield). LCMS: RT=3.85 min [M+H] 576.1 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm).

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified by prep HPLC (Phenomenex AXIA Luna 75×30 mm, 5μ column eluting with 10-90% ACN/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm)

Sources & evidence

ORD record
ord-8ea46e6a9fc149aca203dd5a11bf62a4
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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