Diisopropylethylamine → [2-(2-Fluoro-6-methoxy-phenyl)-thiazol-4-yl]-(2-methyl-piperidin-1-yl)-methanone

HRID 1990994Notes

Reaction equation

HRID 1990994 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[C:10]1[S:11][CH:12]=[C:13]([C:15]([OH:17])=O)[N:14]=1.[CH2:18]1[C@H:27]2[C@@H:22](CCCC2)[CH2:21][CH2:20][NH:19]1.[CH3:28]CN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[C:10]1[S:11][CH:12]=[C:13]([C:15]([N:19]2[CH2:18][CH2:27][CH2:22][CH2:21][CH:20]2[CH3:28])=[O:17])[N:14]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 11083964trans-DecahydroisoquinolineHCID 589248452-(2-Fluoro-6-methoxy-phenyl)-thiazole-4-carboxylic acid

Product 1

HCID 58924834[2-(2-Fluoro-6-methoxy-phenyl)-thiazol-4-yl]-(2-methyl-piperidin-1-yl)-methanoneYield 17.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

2-(2-Fluoro-6-methoxy-phenyl)-thiazole-4-carboxylic acid (49.5 mg, 0.2 mmol) from the previous step, trans-decahydro-isoquinoline (TCI America, Portland, Oreg.; 27.8 mg, 0.2 mmol), DIPEA (0.1 mL, 0.57 mmol), and PyBrop (103 mg, 0.22 mmol) were mixed in dry DCM (1 mL) and the mixture was left stirring for overnight at room temperature. To the mixture was added water. The DCM layer was separated and the aqueous layer was extracted with DCM twice. The combined DCM layers were dried under vacuum and purified by C-18 reversed phase HPLC with a gradient of 10-100% Acetonitrile/water to give [2-(2-fluoro-6-methoxy-phenyl)-thiazol-4-yl]-(2-methyl-piperidin-1-yl)-methanone (12 mg, 16%).

Workup

  1. waitthe mixture was left
  2. customThe DCM layer was separated
  3. extractionthe aqueous layer was extracted with DCM twice
  4. dry with materialThe combined DCM layers were dried under vacuum
  5. custompurified by C-18

Sources & evidence

ORD record
ord-294ddf8108ee4196baab1c4ee00a1295
Source dataset
uspto-grants-2010_01
Patent number
US07645773B2

Reaction notes

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