tert-Butanol → [5-(6-Chloropyridazin-3-yl)-3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl](2-trifluoromethylphenyl)methanone

HRID 1186779Notes

Reaction equation

HRID 1186779 reaction equation
FC(F)(F)C(O)=O.[CH2:8]1[C:12]2[CH2:13][NH:14][CH2:15][C:11]=2[CH2:10][N:9]1[C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]([F:27])([F:26])[F:25])=[O:17].CC(C)([O-])C.[K+].C(O)(C)(C)C.[Cl:39][C:40]1[N:41]=[N:42][C:43](Cl)=[CH:44][CH:45]=1>CN1C(=O)CCC1.C(OCC)(=O)C.O>[Cl:39][C:40]1[N:41]=[N:42][C:43]([N:14]2[CH2:13][C:12]3[CH2:8][N:9]([C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[C:24]([F:27])([F:25])[F:26])=[O:17])[CH2:10][C:11]=3[CH2:15]2)=[CH:44][CH:45]=1

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 673313,6-Dichloropyridazine2×HCID 23665647Potassium tert-butoxideHCID 86661599(3,4,5,6-Tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl)(2-trifluoromethylphenyl)methanone trifluoroacetate

Product 1

HCID 58075182[5-(6-Chloropyridazin-3-yl)-3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl](2-trifluoromethylphenyl)methanone

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

(3,4,5,6-Tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl)(2-trifluoromethylphenyl)methanone trifluoroacetate (1 g, 2.52 mmol, example 1b) was dissolved in 18 ml of NMP and admixed with potassium tert-butoxide (849 mg, 7.57 mmol). tert-Butanol formed was drawn off on a rotary evaporator, and 3,6-dichloropyridazine (376 mg, 2.52 mmol) was added. The reaction mixture was stirred in a microwave reactor at 100° C. for 10 min. After adding 0.5 eq of 3,6-dichloropyridazine each time, the mixture was stirred twice more at 100° C. for 15 min in the microwave reactor. The residue was admixed with water and ethyl acetate, and the organic phase was removed, concentrated and purified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 669 mg (67%), M+H+: 395.08.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred twice more at 100° C. for 15 min in the microwave reactor
  3. customthe organic phase was removed
  4. concentrationconcentrated
  5. custompurified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA)

Sources & evidence

ORD record
ord-6fb3de658de348a4a55446a4d43f6acb
Source dataset
uspto-grants-2014_03
Patent number
US08673917B2

Reaction notes

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