Water → 4-[5-[2-(Difluoromethyl)-4-methoxybenzimidazol-1-yl]-3-(1-methylsulfonylpiperidin-4-yl)triazolo[4,5-d]pyrimidin-7-yl]morpholine

HRID 516420Notes

Reaction equation

HRID 516420 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][CH:7]([F:40])[C:8]1[N:12]([C:13]2[N:14]=[C:15]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:16]3[N:21]=[N:20][N:19]([CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[C:17]=3[N:18]=2)[C:11]2[CH:34]=[CH:35][CH:36]=[C:37]([O:38][CH3:39])[C:10]=2[N:9]=1.C([O-])([O-])=O.[K+].[K+].O>C(Cl)Cl>[F:40][CH:7]([F:6])[C:8]1[N:12]([C:13]2[N:14]=[C:15]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[C:16]3[N:21]=[N:20][N:19]([CH:22]4[CH2:23][CH2:24][N:25]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:26][CH2:27]4)[C:17]=3[N:18]=2)[C:11]2[CH:34]=[CH:35][CH:36]=[C:37]([O:38][CH3:39])[C:10]=2[N:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 666981775-[2-(Difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-7-(4-morpholinyl)-3-(4-piperidinyl)-3h-[1,2,3]triazolo[4,5-d]pyrimidine

Product 1

HCID 469176544-[5-[2-(Difluoromethyl)-4-methoxybenzimidazol-1-yl]-3-(1-methylsulfonylpiperidin-4-yl)triazolo[4,5-d]pyrimidin-7-yl]morpholineYield 87.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (0.09 mL, 1.16 mmol) was added dropwise to a mixture of the above amine (107 mg, 0.220 mmol) and powdered K2CO3 (274 mg, 1.98 mmol) in CH2Cl2 (10 mL) at 0° C. The mixture was allowed to warm to room temperature and was stirred for 16.5 hrs. Water was added, the phases were separated, and the aqueous phase was extracted with CH2Cl2 (1×). The combined organic extracts were dried (Na2SO4) and the solvent removed under vacuum. Recrystallization from CH2Cl2/MeOH gave 5-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-3-[1-(methylsulfonyl)-4-piperidinyl]-7-(4-morpholinyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine (108 mg, 87%): mp 258-259° C.; 1H NMR (CDCl3) δ 7.81 (dd, J=8.4, 0.5 Hz, 1H), 7.41 (t, JHF=53.5 Hz, 1H), 7.39 (t, J=8.2 Hz, 1H), 6.84 (d, J=7.7 Hz, 1H), 4.93 (tt, J=10.5, 4.2 Hz, 1H), 4.79 (br s, 2H), 4.16 (br s, 2H), 4.07 (s, 3H), 4.01-3.90 (m, 6H), 3.14 (m, 2H), 2.89 (s, 3H), 2.60 (m, 2H), 2.35 (m, 2H); Anal. Calcd. for C23H27F2N9O4S: C, 49.0; H, 4.8; N, 22.4. Found: C, 48.9; H, 4.8; N, 22.2%.

Workup

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with CH2Cl2 (1×)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. customthe solvent removed under vacuum
  5. customRecrystallization from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-8cab3db4238941da8af6404ea665818e
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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