Sodium hydride → {5-[6-(Thiazol-2-ylmethoxy)pyridazin-3-yl]-3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl}-(2-trifluoromethylphenyl)methanone

HRID 1186780Notes

Reaction equation

HRID 1186780 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][OH:7].[H-].[Na+].Cl[C:11]1[N:16]=[N:15][C:14]([N:17]2[CH2:21][C:20]3[CH2:22][N:23]([C:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[C:33]([F:36])([F:35])[F:34])=[O:26])[CH2:24][C:19]=3[CH2:18]2)=[CH:13][CH:12]=1>CN(C=O)C>[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][O:7][C:11]1[N:16]=[N:15][C:14]([N:17]2[CH2:18][C:19]3[CH2:24][N:23]([C:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[C:33]([F:34])([F:36])[F:35])=[O:26])[CH2:22][C:20]=3[CH2:21]2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27952131,3-Thiazol-2-ylmethanolHCID 58075182[5-(6-Chloropyridazin-3-yl)-3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl](2-trifluoromethylphenyl)methanone

Product 1

HCID 58075186{5-[6-(Thiazol-2-ylmethoxy)pyridazin-3-yl]-3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl}-(2-trifluoromethylphenyl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Thiazol-2-ylmethanol (64 mg, 0.56 mmol) was dissolved in 2 ml of anhydrous DMF. After adding sodium hydride (42 mg, 55 percent suspension in oil), the mixture was stirred for 30 min, [5-(6-chloropyridazin-3-yl)-3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl](2-trifluoromethylphenyl)methanone (100 mg, 0.25 mmol) was added, and the mixture was stirred at 150° C. for 30 h. After concentrating, water and ethyl acetate were added, and the organic phase was removed, concentrated and purified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 6 mg (5%), M+H+: 474.01.

Workup

  1. stirringthe mixture was stirred at 150° C. for 30 h
  2. concentrationAfter concentrating
  3. additionwater and ethyl acetate were added
  4. customthe organic phase was removed
  5. concentrationconcentrated
  6. custompurified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA)

Sources & evidence

ORD record
ord-28ddd7b2cb724a8e8f238fb1a33f495f
Source dataset
uspto-grants-2014_03
Patent number
US08673917B2

Reaction notes

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