Water → HCID 46917866, compound

HRID 516348Notes

Reaction equation

HRID 516348 reaction equation
[F:1][CH:2]([F:32])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:11]=[C:10]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:5]=2[N:4]=1.C([O-])([O-])=O.[K+].[K+].[CH3:39][S:40](Cl)(=[O:42])=[O:41].O>C(Cl)Cl>[F:32][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:9]=[C:10]([N:20]3[CH2:25][CH2:24][N:23]([S:40]([CH3:39])(=[O:42])=[O:41])[CH2:22][CH2:21]3)[CH:11]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:13]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:5]=2[N:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66698125HCID 66698125, compound

Product 1

HCID 46917866HCID 46917866, compoundYield 67.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 0.223 g (0.5 mmol) of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(1-piperazinyl)-2-pyrimidinyl]-1H-benzimidazole (WO 2008/032064) and 0.345 g (2.5 mmol) of powdered K2CO3 in 20 mL CH2Cl2 was cooled to 0° C., and 0.086 g (0.75 mmol) of methanesulfonyl chloride was added. The reaction mixture was allowed to warm to room temperature, and after stirring overnight water was added. The organic layer was separated, washed successively with aqueous acetic acid and aq. ammonia, and dried. Chromatography on silica, eluting with CH2Cl2/EtOAc (4:1) gave 0.176 g (67% yield) of 2-(difluoromethyl)-4-methoxy-1-[4-[4-(methylsulfonyl)-1-piperazinyl]-6-(4-morpholinyl)-2-pyrimidinyl]-1H-benzimidazole: mp (MeOH) 273-274° C.; 1H NMR (CDCl3) δ7.74 (dd, J=8.4, 0.6 Hz, 1H), 7.38 (t, JHF=53.5 Hz, 1H), 7.33 (t, J=8.2 Hz, 1H), 6.79 (t, J=7.6 Hz, 1H), 5.54 (s, 1H), 4.05 (s, 3H), 3.83-3.79 (m, 8H), 3.64 (m, 4H), 3.35 (m, 4H), 2.82 (s, 3H); Anal. Calcd. for C22H27F2N7O4S: C, 50.5; H, 5.2; N, 18.7. Found: C, 50.7; H, 5.3; N, 18.75%.

Workup

  1. additionwas added
  2. customThe organic layer was separated
  3. washwashed successively with aqueous acetic acid and aq. ammonia
  4. customdried
  5. washChromatography on silica, eluting with CH2Cl2/EtOAc (4:1)

Sources & evidence

ORD record
ord-542f443b41b743718f9019dd8806ceb4
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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