Water → 3-[2-(3-Trifluoromethyl-phenoxy)-ethylamino]-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

HRID 550826Notes

Reaction equation

HRID 550826 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:11]=[C:10]([NH:12][C:13]([N:15]3[CH2:19][CH2:18][C@H:17]([NH2:20])[CH2:16]3)=[O:14])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1.C(N(CC)C(C)C)(C)C.Br[CH2:31][CH2:32][O:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=1.O>CN(C)C=O>[CH3:1][O:2][C:3]1[C:4]2[N:11]=[C:10]([NH:12][C:13]([N:15]3[CH2:19][CH2:18][CH:17]([NH:20][CH2:31][CH2:32][O:33][C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:41])([F:42])[F:43])[CH:35]=4)[CH2:16]3)=[O:14])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27733141-(2-Bromoethoxy)-3-(trifluoromethyl)benzeneHCID 59011943(S)-3-amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

Product 1

HCID 248302883-[2-(3-Trifluoromethyl-phenoxy)-ethylamino]-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amideYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-3-amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (300 mg, 0.74 mmol) in N,N-dimethylformamide (5 mL) was treated with N,N-diisopropylethylamine (285 mg, 2.20 mmol) and 1-(2-bromoethoxy)-3-(trifluoromethyl) benzene (220 mg, 0.81 mmol). The reaction mixture was allowed to stir at 80° C. for 1 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. Preparative high pressure liquid chromatography afforded 3-[2-(3-trifluoromethyl-phenoxy)-ethylamino]-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (28 mg, 8%) as a light brown solid; LRMS for C20H21F3N6O3S (M+H)+ at m/z=482. 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-e3cce35db069491785801e1c70e5ece5
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

Loading…