Sodium Cyanide → HCID 23582535, compound

HRID 238749Notes

Reaction equation

HRID 238749 reaction equation
Br[CH2:2][C:3]1([NH:6][C:7]([NH:9][C@@:10]([C:25]2[CH:30]=[C:29]([O:31][C:32]([F:37])([F:36])[CH:33]([F:35])[F:34])[CH:28]=[C:27]([F:38])[CH:26]=2)([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:8])[CH2:5][CH2:4]1.[C-:39]#[N:40].[Na+]>CS(C)=O>[C:39]([CH2:2][C:3]1([NH:6][C:7]([NH:9][C@@:10]([C:25]2[CH:30]=[C:29]([O:31][C:32]([F:37])([F:36])[CH:33]([F:35])[F:34])[CH:28]=[C:27]([F:38])[CH:26]=2)([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:8])[CH2:5][CH2:4]1)#[N:40]

Participants

4

Reactant 2

HCID 8929Sodium CyanideHCID 58897958HCID 58897958, compound

Product 1

HCID 23582535HCID 23582535, compoundYield 70.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of (R)-1-(1-(bromomethyl)cyclopropyl)-3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea (8 mg, 0.013 mmol) in DMSO (0.3 mL) was added NaCN (18 mg, 0.37 mmol) and KI (20 mg, 0.12 mmol). The reaction mixture was stirred at rt for 3 days. The reaction mixture was concentrated under reduced pressure and purified by preparative HPLC (Phenomenex AXIA Luna column, 30×100 mm, flow rate 40 mL/min, 30-100% ACN/H2O/0.1% TFA over 12 min) to yield (R)-1-(1-(cyanomethyl)cyclopropyl)-3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea (Example 242, 5 mg, 63% yield). LCMS: RT=3.88 min [M+H]548.3 (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); 1H NMR (400 MHz, CDCl3) ppm 0.76-0.91 (m, 4H), 2.58 (qt, J=17 Hz, 2H), 3.78 (qt, J=12 Hz, 2H), 5.49 (s, 1H), 5.52 (s, 1H), 5.87 (t, J=53 Hz, 1H), 6.66 (d, J=6.6 Hz, 2H), 6.84-6.95 (m, 3H), 6.96-7.07 (m, 2H), 7.07-7.26 (m, 5H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. custompurified by preparative HPLC (Phenomenex AXIA Luna column, 30×100 mm, flow rate 40 mL/min, 30-100% ACN/H2O/0.1% TFA over 12 min)

Sources & evidence

ORD record
ord-b7e6d9e50d4a417f9d1480b539f699c4
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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