Water → 4-(4-Chloro-2-methanesulfonyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

HRID 550812Notes

Reaction equation

HRID 550812 reaction equation
Cl.[CH3:2][O:3][C:4]1[C:5]2[N:12]=[C:11]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[O:15])[S:10][C:6]=2[N:7]=[CH:8][N:9]=1.C(N(CC)C(C)C)(C)C.Br[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=1[S:40]([CH3:43])(=[O:42])=[O:41].O>CN(C)C=O>[CH3:2][O:3][C:4]1[C:5]2[N:12]=[C:11]([NH:13][C:14]([N:16]3[CH2:17][CH2:18][N:19]([CH2:32][C:33]4[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=4[S:40]([CH3:43])(=[O:42])=[O:41])[CH2:20][CH2:21]3)=[O:15])[S:10][C:6]=2[N:7]=[CH:8][N:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27610541-(Bromomethyl)-4-chloro-2-(methylsulfonyl)benzeneHCID 86616506Piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride

Product 1

HCID 248317194-(4-Chloro-2-methanesulfonyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amideYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride (as prepared in Example 1, 625 mg, 1.70 mmol) in N,N-dimethylformamide (5 mL) was treated with N,N-diisopropylethylamine (660 mg, 5.10 mmol) followed by 1-(bromomethyl)-4-chloro-2-(methylsulfonyl)-benzene (530 mg, 1.87 mmol). The reaction mixture was allowed to stir at 80° C. for 3 h. At this time, the reaction was poured into water. The aqueous layer was extracted with ethyl acetate. The organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexanes/ethyl acetate) afforded 4-(4-chloro-2-methanesulfonyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (580 mg, 69%) as an off-white solid; LRMS for C19H21ClN6O4S2 (M+H)+ at m/z=496. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate
  2. washThe organics were washed with a saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eecf251d419c45ce90c6916df1bf409d
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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