Methyl iodide → HCID 23582802, compound

HRID 1874185Notes

Reaction equation

HRID 1874185 reaction equation
[N:1]1[NH:2][N:3]=[N:4][C:5]=1[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][NH:11][C:12]([NH:14][C@@:15]([C:30]1[CH:35]=[C:34]([O:36][C:37]([F:42])([F:41])[CH:38]([F:40])[F:39])[CH:33]=[C:32]([F:43])[CH:31]=1)([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:13].[C:44]([O-])([O-])=O.[K+].[K+].CI>CC#N>[F:43][C:32]1[CH:31]=[C:30]([C@:15]([NH:14][C:12]([NH:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:5]2[N:4]=[N:3][N:2]([CH3:44])[N:1]=2)=[O:13])([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:35]=[C:34]([O:36][C:37]([F:42])([F:41])[CH:38]([F:40])[F:39])[CH:33]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 59459380HCID 59459380, compound

Product 1

HCID 23582802HCID 23582802, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (R)-1-(5-(2H-tetrazol-5-yl)pentyl)-3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea (12 mg, 0.019 mmol) in MeCN (115 μl) at rt was added K2CO3 (3.2 mg, 0.023 mmol) followed by MeI (1.5 μL, 0.023 mmol). The reaction mixture was heated to 80° C. overnight. The reaction mixture was quenched by addition of H2O and the aqueous layer was extracted with EtOAc (3×). The combined organic layers were concentrated and the residue was dissolved in MeOH and purified by preparative HPLC (Phenoma Luna AXIA 10A, C18, eluting with MeCN/H2O containing 0.1% TFA, monitoring at 220 nm) to provide (R)-1-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(5-(2-methyl-2H-tetrazol-5-yl)pentyl)urea (Example 260, 2 mg, 18% yield) as white solid. 1H NMR (500 MHz, CDCl3) ppm 7.17-7.08 (m, 5H), 6.99-6.85 (m, 5H), 6.67 (d, J=5 Hz, 2 H), 5.98-5.75 (m, 1H), 4.23 (s, 3H), 3.82 (d, J=15 Hz, 1H), 3.68 (d, J=15 Hz, 1H), 3.10-3.07 (m, 2H), 2.85-2.82 (m, 2H), 1.77-1.71 (m, 2H), 1.46-1.40 (m, 2H), 1.32-1.26 (m, 2H); LC/MS: RT=3.218 min [M+H] 621.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeCN/H2O over 4 minutes containing 0.1% NH4OAc; 4 mL/min, monitoring at 220 nm).

Workup

  1. customThe reaction mixture was quenched by addition of H2O
  2. extractionthe aqueous layer was extracted with EtOAc (3×)
  3. concentrationThe combined organic layers were concentrated
  4. dissolutionthe residue was dissolved in MeOH
  5. custompurified by preparative HPLC (Phenoma Luna AXIA 10A, C18, eluting with MeCN/H2O containing 0.1% TFA, monitoring at 220 nm)

Sources & evidence

ORD record
ord-da174db5f3d6443a9b3bad122104c8a0
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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