HCID 178418676, compound → HCID 178519615, compound

HRID 625789Notes

Reaction equation

HRID 625789 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([C:17]([O:19]CC)=O)[N:8]=2)=[N:2]1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([Mg]Br)=[CH:25][CH:24]=1>C1COCC1>[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([C:17]([C:26]3[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=3)([C:26]3[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=3)[OH:19])[N:8]=2)=[N:2]1

Participants

4

Reactant 2

HCID 178418676HCID 178418676, compoundHCID 178470277HCID 178470277, compound

Product 1

HCID 178519615HCID 178519615, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a stirred solution of ethyl 4-(1H-pyrazol-3-ylamino)quinazoline-2-carboxylate (595 mg, 2.1 mmol) in THF (15 mL) at −40° C., was added dropwise a 2 M solution of 4-fluorophenylmagnesium bromide in THF (4.2 mL, 8.4 mmol). The mixture was stirred at −40° C. for 2 h and then stored at −30° C. for 18 h. The reaction was quenched by adding 0.5 N HCl at 0° C. and the mixture was extracted with EtOAc (2×20 mL). The solid precipitate from the combined organic layers was removed by filtration and the resulting filtrate was washed with brine. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography eluting with 0-5% MeOH/DCM to afford (4-(1H-pyrazol-3-ylamino)quinazolin-2-yl)bis(4-fluorophenyl)methanol as a solid (75 mg, 8%). 1H NMR (300 MHz, DMSO-d6) δ 12.50 (s, 1H), 10.66 (s, 1H), 8.67 (d, J=8.1, 1H), 7.81-7.87 (m, 2H), 7.60-7.62 (m, 2H), 7.42-7.47 (m, 4H), 7.07-7.13 (m, 4H), 6.66 (s, 1H), 6.26 (s, 1H); LC-MS (ESI) m/z 430 (M+H)+.

Workup

  1. waitstored at −30° C. for 18 h
  2. customThe reaction was quenched
  3. additionby adding 0.5 N HCl at 0° C.
  4. extractionthe mixture was extracted with EtOAc (2×20 mL)
  5. customThe solid precipitate from the combined organic layers was removed by filtration
  6. washthe resulting filtrate was washed with brine
  7. dry with materialThe organic phase was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by silica gel chromatography
  11. washeluting with 0-5% MeOH/DCM

Sources & evidence

ORD record
ord-d64677ec8af445feb46ead186076eeba
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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