Triethylamine → Methanesulfonic acid 2-[2-[1-(6-amino-5-cyano-pyrimidin-4-yl)-piperidin-4-yl]-4-(4-fluoro-3-trifluoromethyl-phenyl)-imidazol-1-yl]-ethyl ester

HRID 2284062Notes

Reaction equation

HRID 2284062 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]3[N:17]([CH2:32][CH2:33][OH:34])[CH:18]=[C:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=4)[N:20]=3)[CH2:12][CH2:11]2)[N:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[CH3:42][S:43](Cl)(=[O:45])=[O:44]>ClCCl>[NH2:1][C:2]1[N:3]=[CH:4][N:5]=[C:6]([N:10]2[CH2:11][CH2:12][CH:13]([C:16]3[N:17]([CH2:32][CH2:33][O:34][S:43]([CH3:42])(=[O:45])=[O:44])[CH:18]=[C:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=4)[N:20]=3)[CH2:14][CH2:15]2)[C:7]=1[C:8]#[N:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 894426984-Amino-6-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-(2-hydroxy-ethyl)-1H-imidazol-2-yl]-piperidin-1-yl}-pyrimidine-5-carbonitrile

Product 1

HCID 89442673Methanesulfonic acid 2-[2-[1-(6-amino-5-cyano-pyrimidin-4-yl)-piperidin-4-yl]-4-(4-fluoro-3-trifluoromethyl-phenyl)-imidazol-1-yl]-ethyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

4-Amino-6-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-(2-hydroxy-ethyl)-1H-imidazol-2-yl]-piperidin-1-yl}-pyrimidine-5-carbonitrile (22.8 mg; 0.47 mmol; 1.00 eq) was dissolved in dichloromethane (10.00 mL) and chilled to −78° C. The solution was charged with triethylamine (0.20 mL; 1.41 mmol; 3.00 eq) and methanesulfonyl chloride (0.05 mL; 0.70 mmol; 1.50 eq). The reaction was stirred, cold, for 1 hour, then allowed to warm to ambient temperature. The reaction mixture was quenched by dropwise addition of sodium bicarbonate (saturated aq; 10 mL). The organic layer was separated, dried over sodium sulphate, filtered and concentrated to yield methanesulfonic acid 2-[2-[1-(6-amino-5-cyano-pyrimidin-4-yl)-piperidin-4-yl]-4-(4-fluoro-3-trifluoromethyl-phenyl)-imidazol-1-yl]-ethyl ester (259 mg; 0.47 mmol; 99.8%). LC-MS: (M+1=554, obsd.=554).

Workup

  1. temperatureto warm to ambient temperature
  2. customThe reaction mixture was quenched by dropwise addition of sodium bicarbonate (saturated aq; 10 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-832f4735f0a24d7bbb60a614b7f743ad
Source dataset
uspto-grants-2015_09
Patent number
US09145392B2

Reaction notes

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