Methanesulfonyl chloride → HCID 46917725, compound

HRID 1619799Notes

Reaction equation

HRID 1619799 reaction equation
[F:1][CH:2]([F:39])[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)[N:11]=[C:10]([N:20]([CH:27]3[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]3)[CH2:21][CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])[N:9]=2)[C:6]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:5]=2[N:4]=1.CCN(C(C)C)C(C)C.[CH3:49][S:50](Cl)(=[O:52])=[O:51]>C(Cl)Cl>[F:39][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([N:20]([CH:27]3[CH2:32][CH2:31][CH2:30][N:29]([S:50]([CH3:49])(=[O:52])=[O:51])[CH2:28]3)[CH2:21][CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])[N:9]=2)[C:6]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:5]=2[N:4]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67533983HCID 67533983, compound

Product 1

HCID 46917725HCID 46917725, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-N3,N3-dimethyl-N1-(3-piperidinyl)-1,3-propanediamine (155 mg, 0.28 mmol) and DIPEA (1 mL) in CH2Cl2 (10 mL) was added methanesulfonyl chloride (0.5 mL) at 0° C. The resulting mixture was stirred for 16 hrs at room temperature. After dilution with water, the organic layer was separated, and the aqueous layer was further extracted with CH2Cl2 (3×15 mL). The combined organic fractions were dried over Na2SO4, and the solvent removed under vacuum. The residue was chromatographed on alumina eluting with CH2Cl2/MeOH (97:3) to give partially pure material, which was further purified by chromatography on silica eluting with CH2Cl2/MeOH (97:3) to give N1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-N3,N3-dimethyl-N1-[1-(methylsulfonyl)-3-piperidinyl]-1,3-propanediamine (125 mg, 72% yield).

Workup

  1. customAfter dilution with water, the organic layer was separated
  2. extractionthe aqueous layer was further extracted with CH2Cl2 (3×15 mL)
  3. dry with materialThe combined organic fractions were dried over Na2SO4
  4. customthe solvent removed under vacuum
  5. customThe residue was chromatographed on alumina eluting with CH2Cl2/MeOH (97:3)
  6. customto give partially pure material, which
  7. customwas further purified by chromatography on silica eluting with CH2Cl2/MeOH (97:3)

Sources & evidence

ORD record
ord-5754df9c97814872ac0995c8172869cd
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

Loading…