HCID 67111742, compound → 1-(2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)thiazolo[5,4-b]pyridin-5-yl)-1-(3,3-difluorocyclobutyl)-2-(trimethylsilyl)ethanol

HRID 1177596Notes

Reaction equation

HRID 1177596 reaction equation
[CH3:1][Si:2]([CH2:5][Mg]Cl)([CH3:4])[CH3:3].[O:8]1[CH2:13][CH2:12][CH2:11][O:10][CH:9]1[C:14]1[CH:19]=[CH:18][C:17]([C:20]2[S:21][C:22]3[C:27]([N:28]=2)=[CH:26][CH:25]=[C:24]([C:29]([CH:31]2[CH2:34][C:33]([F:36])([F:35])[CH2:32]2)=[O:30])[N:23]=3)=[C:16]([F:37])[CH:15]=1>C1COCC1>[O:10]1[CH2:11][CH2:12][CH2:13][O:8][CH:9]1[C:14]1[CH:19]=[CH:18][C:17]([C:20]2[S:21][C:22]3[C:27]([N:28]=2)=[CH:26][CH:25]=[C:24]([C:29]([CH:31]2[CH2:32][C:33]([F:36])([F:35])[CH2:34]2)([OH:30])[CH2:5][Si:2]([CH3:3])([CH3:4])[CH3:1])[N:23]=3)=[C:16]([F:37])[CH:15]=1

Participants

4

Reactant 2

HCID 67111742HCID 67111742, compoundHCID 178418680HCID 178418680, compound

Product 1

HCID 671117021-(2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)thiazolo[5,4-b]pyridin-5-yl)-1-(3,3-difluorocyclobutyl)-2-(trimethylsilyl)ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Trimethylsilylmethylmagnesium chloride (1.1M solution in THF; 2.24 mL, 2.47 mmol) was added to a solution of (2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)thiazolo[5,4-b]pyridin-5-yl)(3,3-difluorocyclobutyl)methanone (630 mg, 1.450 mmol) in THF (30.0 mL) at 25° C., and the resulting solution was stirred at 25° C. for 10 min. Excess Grignard reagent was quenched by the careful addition of sat. aq. NH4Cl (10 mL), water was added to dissolve the precipitated salts, and THF was then removed in vacuo. The resulting mixture was partitioned between EtOAc (250 mL) and sat. aq. NH4Cl (50 mL), and the organic layer was separated and washed with brine (50 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to provide 1-(2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)thiazolo[5,4-b]pyridin-5-yl)-1-(3,3-difluoro-cyclobutyl)-2-(trimethylsilyl)ethanol as a yellow foam. MS (ESI) m/z: Calculated: 522.2; Observed: 522.8 (M++1).

Workup

  1. customExcess Grignard reagent was quenched by the careful addition of sat. aq. NH4Cl (10 mL), water
  2. additionwas added
  3. dissolutionto dissolve the precipitated salts, and THF
  4. customwas then removed in vacuo
  5. customThe resulting mixture was partitioned between EtOAc (250 mL) and sat. aq. NH4Cl (50 mL)
  6. customthe organic layer was separated
  7. washwashed with brine (50 mL)
  8. dry with materialThe organic layer was then dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b47a0f5814514b3497bace87ad9b7afc
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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