Diisopropylethylamine → (R)-4-(7-chloro-5-cyclopropyl-thiazolo[4,5-d]pyrimidin-2-yl)-1-(4-cyclopropyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamide

HRID 908648Notes

Reaction equation

HRID 908648 reaction equation
[F:1][C:2]([F:33])([F:32])[O:3][C:4]1[CH:31]=[CH:30][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][NH:16][CH2:15][CH2:14][N:13]2[S:18]([C:21]2[CH:26]=[CH:25][C:24]([CH:27]3[CH2:29][CH2:28]3)=[CH:23][CH:22]=2)(=[O:20])=[O:19])=[O:11])=[CH:6][CH:5]=1.Cl[C:35]1[S:36][C:37]2[C:42]([Cl:43])=[N:41][C:40]([CH:44]3[CH2:46][CH2:45]3)=[N:39][C:38]=2[N:47]=1.C(N(CC)C(C)C)(C)C>C(Cl)(Cl)Cl.C(OCC)(=O)C>[F:33][C:2]([F:1])([F:32])[O:3][C:4]1[CH:31]=[CH:30][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][N:16]([C:35]3[S:36][C:37]4[C:42]([Cl:43])=[N:41][C:40]([CH:44]5[CH2:45][CH2:46]5)=[N:39][C:38]=4[N:47]=3)[CH2:15][CH2:14][N:13]2[S:18]([C:21]2[CH:26]=[CH:25][C:24]([CH:27]3[CH2:28][CH2:29]3)=[CH:23][CH:22]=2)(=[O:19])=[O:20])=[O:11])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 597037622,7-Dichloro-5-cyclopropyl-thiazolo[4,5-d]pyrimidineHCID 59703776(R)-1-(4-cyclopropyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamide

Product 1

HCID 59703855(R)-4-(7-chloro-5-cyclopropyl-thiazolo[4,5-d]pyrimidin-2-yl)-1-(4-cyclopropyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamideYield 96.6%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (R)-1-(4-cyclopropyl-benzenesulfonyl)-piperazine-2-carboxylic acid 4-trifluoromethoxy-benzylamide (39 mg) obtained in Example 1100, Step 4 and 2,7-dichloro-5-cyclopropyl-thiazolo [4,5-d]pyrimidine (20 mg) in chloroform (1.0 ml) was added N,N-diisopropylethylamine (20 μl) at room temperature. After stirring overnight at room temperature, the reaction mixture was diluted with ethyl acetate, and the mixture was partitioned by adding water. The organic layer was dried over anhydrous sodium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1) to give the title compound (54 mg).

Workup

  1. customthe mixture was partitioned
  2. additionby adding water
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltrated
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:1)

Sources & evidence

ORD record
ord-a9709734a0da4473aac388ad367aee99
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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