Diisopropylethylamine → (R)-4-(7-chloro-5-trifluoromethyl-thiazolo[4,5-d]pyrimidin-2-yl)-1-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-2-carboxylic acid 4-difluoromethoxy-3-fluoro-benzylamide

HRID 908621Notes

Reaction equation

HRID 908621 reaction equation
[F:1][CH:2]([F:35])[O:3][C:4]1[CH:33]=[CH:32][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]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=2)(=[O:20])=[O:19])=[O:11])=[CH:6][C:5]=1[F:34].C(N(CC)C(C)C)(C)C.Cl[C:46]1[S:47][C:48]2[C:53]([Cl:54])=[N:52][C:51]([C:55]([F:58])([F:57])[F:56])=[N:50][C:49]=2[N:59]=1>C(Cl)(Cl)Cl>[F:35][CH:2]([F:1])[O:3][C:4]1[CH:33]=[CH:32][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][N:16]([C:46]3[S:47][C:48]4[C:53]([Cl:54])=[N:52][C:51]([C:55]([F:58])([F:57])[F:56])=[N:50][C:49]=4[N:59]=3)[CH2:15][CH2:14][N:13]2[S:18]([C:21]2[CH:22]=[CH:23][C:24]([O:27][C:28]([F:29])([F:31])[F:30])=[CH:25][CH:26]=2)(=[O:20])=[O:19])=[O:11])=[CH:6][C:5]=1[F:34]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 597038262,7-Dichloro-5-trifluoromethyl-thiazolo[4,5-d]pyrimidineHCID 59703843(R)-1-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-2-carboxylic acid 4-difluoromethoxy-3-fluoro-benzylamide

Product 1

HCID 59703768(R)-4-(7-chloro-5-trifluoromethyl-thiazolo[4,5-d]pyrimidin-2-yl)-1-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-2-carboxylic acid 4-difluoromethoxy-3-fluoro-benzylamideYield 79%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of the compound (796 mg) obtained in Step 5 in chloroform (8 ml) were successively added, with stirring under ice-cooling, N,N-diisopropylethylamine (234 mg) and 2,7-dichloro-5-trifluoromethyl-thiazolo[4,5-d]pyrimidine (414 mg). After stirring at room temperature for 1 hr, the mixture was partitioned by adding chloroform and water. The aqueous layer was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=6:1-1:2) to give the title compound (912 mg).

Workup

  1. temperaturecooling
  2. stirringAfter stirring at room temperature for 1 hr
  3. customthe mixture was partitioned
  4. additionby adding chloroform and water
  5. extractionThe aqueous layer was extracted with chloroform
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=6:1-1:2)

Sources & evidence

ORD record
ord-4229400c0e2044e4adc9cb961e34caba
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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