Methanol → (R)-4-(5-methyl-4-oxo-4,5-dihydro-thiazolo[4,5-d]pyridazin-2-yl)-1-(4-trifluoromethyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamide

HRID 908643Notes

Reaction equation

HRID 908643 reaction equation
[F:1][C:2]([F:44])([F:43])[O:3][C:4]1[CH:42]=[CH:41][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][N:16]([C:18]3[S:19][C:20]4[CH:25]=[N:24][NH:23][C:22](=[O:26])[C:21]=4[N:27]=3)[CH2:15][CH2:14][N:13]2[S:28]([C:31]2[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=2)(=[O:30])=[O:29])=[O:11])=[CH:6][CH:5]=1.CO.[C:47]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[F:44][C:2]([F:1])([F:43])[O:3][C:4]1[CH:42]=[CH:41][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][N:16]([C:18]3[S:19][C:20]4[CH:25]=[N:24][N:23]([CH3:47])[C:22](=[O:26])[C:21]=4[N:27]=3)[CH2:15][CH2:14][N:13]2[S:28]([C:31]2[CH:36]=[CH:35][C:34]([C:37]([F:38])([F:39])[F:40])=[CH:33][CH:32]=2)(=[O:30])=[O:29])=[O:11])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 887Methanol2×HCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 59703772(R)-4-(4-oxo-4,5-dihydro-thiazolo[4,5-d]pyridazin-2-yl)-1-(4-trifluoromethyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamide

Product 1

HCID 59703794(R)-4-(5-methyl-4-oxo-4,5-dihydro-thiazolo[4,5-d]pyridazin-2-yl)-1-(4-trifluoromethyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamideYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the compound (40 mg) obtained in Step 6 in THF (0.8 ml) were added methanol (3.7 μl), triphenylphosphine (24 mg) and diisopropyl azodicarboxylate (18 μl) with stirring under ice-cooling, and the mixture was stirred overnight at room temperature. Methanol (1.2 μl), triphenylphosphine (8 mg) and diisopropyl azodicarboxylate (6 μl) was added at room temperature, and the mixture was stirred for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol:chloroform=5:95) to give the title compound (29 mg).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred overnight at room temperature
  3. stirringthe mixture was stirred for 3 hr
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (methanol:chloroform=5:95)

Sources & evidence

ORD record
ord-53780b552b1f4f1d95c2b14b80698821
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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