Dimethylformamide → 4-(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenylamino)butanoic acid

HRID 1177565Notes

Reaction equation

HRID 1177565 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8](F)[CH:7]=[CH:6][C:5]=1[C:11]1[S:12][C:13]2[C:18]([N:19]=1)=[CH:17][CH:16]=[C:15]([C:20]1([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:22][CH2:21]1)[N:14]=2.[NH:29]1[CH2:33][CH2:32][CH2:31][C:30]1=[O:34].CN(C=[O:39])C>>[F:3][C:4]1[CH:9]=[C:8]([NH:29][CH2:33][CH2:32][CH2:31][C:30]([OH:34])=[O:39])[CH:7]=[CH:6][C:5]=1[C:11]1[S:12][C:13]2[C:18]([N:19]=1)=[CH:17][CH:16]=[C:15]([C:20]1([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:21][CH2:22]1)[N:14]=2

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 120252-Pyrrolidone2×HCID 24758Sodium hydride2×HCID 671117902-(2,4-Difluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Product 1

HCID 445996874-(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenylamino)butanoic acid

Conditions

Temperature
25 °C

Procedure

Sodium hydride (60% w/w in mineral oil) (3.7 mg, 93 μmol) was added to a mixture of 2-(2,4-difluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (28.2 mg, 77 μmol) and pyrrolidin-2-one (5.9 μl, 77 μmol) in DMF (0.8 mL) and the resulting mixture was stirred at 25° C. for 30 min, then heated at 40° C. for 15 h. Additional pyrrolidin-2-one (5.9 μl, 77 μmol) and sodium hydride (60% w/w in mineral oil) (3.7 mg, 93 μmol) were then added, and the resulting mixture was heated at 60° C. for 1 h. The reaction mixture was then cooled to 25° C. and partitioned between EtOAc (70 mL) and sat. aq. ammonium chloride (30 mL). The organic layer was separated and sequentially washed with water and brine, then dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% EtOAc-Hexanes) provided 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenylamino)butanoic acid as a light yellow solid. MS (ESI) m/z: Calculated: 447.1; Observed: 448.2 (M++1).

Workup

  1. temperatureheated at 40° C. for 15 h
  2. temperaturethe resulting mixture was heated at 60° C. for 1 h
  3. temperatureThe reaction mixture was then cooled to 25° C.
  4. custompartitioned between EtOAc (70 mL) and sat. aq. ammonium chloride (30 mL)
  5. customThe organic layer was separated
  6. washsequentially washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customChromatographic purification of the residue (silica gel, 0-100% EtOAc-Hexanes)

Sources & evidence

ORD record
ord-82979b7197ea467ab359d063ef4fb678
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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