Hydrochloric Acid → Diethyl 2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenethyl)malonate

HRID 1177609Notes

Reaction equation

HRID 1177609 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[C:7]([O:15][CH2:16][CH3:17])(=[O:14])[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].[F:18][C:19]1[CH:24]=[C:23]([CH:25]=[CH2:26])[CH:22]=[CH:21][C:20]=1[C:27]1[S:28][C:29]2[C:34]([N:35]=1)=[CH:33][CH:32]=[C:31]([C:36]1([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH2:38][CH2:37]1)[N:30]=2.Cl>CN(C=O)C>[F:18][C:19]1[CH:24]=[C:23]([CH:22]=[CH:21][C:20]=1[C:27]1[S:28][C:29]2[C:34]([N:35]=1)=[CH:33][CH:32]=[C:31]([C:36]1([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH2:38][CH2:37]1)[N:30]=2)[CH2:25][CH2:26][CH:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:7]([O:15][CH2:16][CH3:17])=[O:14]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 10796Cesium carbonateHCID 591749092-(2-Fluoro-4-vinylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Product 1

HCID 67111704Diethyl 2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenethyl)malonate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In reactor bottle under N2 were combined fine cesium carbonate (0.209 g, 0.644 mmol) and diethyl malonate (0.195 mL, 1.29 mmol) in DMF (3 mL). The resulting slurry was allowed to stir for 1 h at ambient temperature. To the mixture was added 2-(2-fluoro-4-vinylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (0.200 g, 0.537 mmol) and the reaction mixture was heated to 35° C. for 1.5 h. The reaction mixture was cooled to 0° C. and acidified using 1 N aq. HCl, extracted with EtOAc, and the organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography provided diethyl 2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenethyl)malonate. MS (ESI) m/z: calculated: 532.2; Observed: 533.1 (M++1).

Workup

  1. customIn reactor bottle under N2 were combined fine
  2. temperaturethe reaction mixture was heated to 35° C. for 1.5 h
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. extractionextracted with EtOAc
  5. dry with materialthe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-c8e7ca8183e54436b3d56a28fe56a3c7
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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