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

HRID 908626Notes

Reaction equation

HRID 908626 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][C:33]([F:36])([F:35])[F:34])[CH2:6][NH:7][C:8]([C@H:10]1[CH2:15][NH:14][CH2:13][CH2:12][N:11]1[S:16]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)(=[O:18])=[O:17])=[O:9].Cl[C:38]1[S:39][C:40]2[C:45]([Cl:46])=[N:44][C:43]([CH:47]3[CH2:49][CH2:48]3)=[N:42][C:41]=2[N:50]=1.C(N(CC)C(C)C)(C)C>C(Cl)(Cl)Cl>[F:2][C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][C:33]([F:36])([F:34])[F:35])[CH2:6][NH:7][C:8]([C@H:10]1[CH2:15][N:14]([C:38]2[S:39][C:40]3[C:45]([Cl:46])=[N:44][C:43]([CH:47]4[CH2:48][CH2:49]4)=[N:42][C:41]=3[N:50]=2)[CH2:13][CH2:12][N:11]1[S:16]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)(=[O:17])=[O:18])=[O:9]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 597037622,7-Dichloro-5-cyclopropyl-thiazolo[4,5-d]pyrimidineHCID 86619482(R)-1-(4-trifluoromethyl-benzenesulfonyl)-piperazine-2-carboxylic acid 3-fluoro-4-trifluoromethoxy-benzylamide hydrochloride

Product 1

HCID 59703761(R)-4-(7-chloro-5-cyclopropyl-thiazolo[4,5-d]pyrimidin-2-yl)-1-(4-trifluoromethyl-benzenesulfonyl)-piperazine-2-carboxylic acid 3-fluoro-4-trifluoromethoxy-benzylamideYield 74.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of the crude product (about 0.095 mmol) obtained in Step 5 and 2,7-dichloro-5-cyclopropyl-thiazolo[4,5-d]pyrimidine (24 mg) in chloroform (1.0 ml) was added N,N-diisopropylethylamine (42 μl) at room temperature. After stirring at room temperature for 2 hr, the reaction mixture was concentrated under reduced pressure, and the residue was purified by thin layer silica gel chromatography (methanol:chloroform=1:10) to give the title compound (52 mg). 1H-NMR (CDCl3, 300 MHz) δ: 1.03-1.09 (2H, m), 1.17-1.22 (2H, m), 2.18-2.27 (1H, m), 3.14-3.35 (2H, m), 3.43-3.53 (1H, m), 3.96 (1H, d, J=13.6 Hz), 4.22-4.36 (2H, m), 4.45-4.69 (3H, m), 6.97-7.06 (3H, m), 7.20 (1H, t, J=8.5 Hz), 7.83 (2H, d, J=8.3 Hz), 8.02 (2H, d, J=8.3 Hz).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by thin layer silica gel chromatography (methanol:chloroform=1:10)

Sources & evidence

ORD record
ord-2137c7df5bd74036bc23f42a995d94fb
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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