HCID 178418676, compound → HCID 178488739, compound

HRID 625771Notes

Reaction equation

HRID 625771 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7]2[C:16]3[C:11](=[C:12]([O:17][CH3:18])[CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([C:19]([O:21]CC)=O)[N:8]=2)=[N:2]1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([Mg]Br)=[CH:27][CH:26]=1>C1COCC1>[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7]2[C:16]3[C:11](=[C:12]([O:17][CH3:18])[CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([C:19]([C:28]3[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=3)=[O:21])[N:8]=2)=[N:2]1

Participants

4

Reactant 2

HCID 178418676HCID 178418676, compoundHCID 178470278HCID 178470278, compound

Product 1

HCID 178488739HCID 178488739, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To ethyl 4-(1H-pyrazol-3-ylamino)-8-methoxyquinazoline-2-carboxylate (200 mg, 0.64 mmol) in dry THF (8 mL) cooled to −40° C. was added dropwise over 2 min 1N 4-fluorophenylmagnesium bromide in THF (2.17 mL, 2.17 mmol). After 1.5 h the reaction mixture was quenched by addition of saturated aq ammonium chloride. The solution was concentrated and H2O was added. The precipitate was washed with water and diethyl ether to give (4-(1H-pyrazol-3-ylamino)-8-methoxyquinazolin-2-yl)(4-fluorophenyl)methanone as a yellow solid (74 mg, 87% purity by LC/MS) 1H NMR (300 MHz, DMSO-d6) δ ppm 3.94 (s, 3H) 6.75 (s, 1H) 7.35-7.41 (m, 3H) 7.58-7.65 (m, 2H) 8.07-8.12 (m, 2H) 8.2 (d, J=8.48 Hz, 1H) 10.64 (br. s., 1H) 12.51 (br. s., 1H) LC-MS (ESI) m/z 364 (M+H)+.

Workup

  1. customAfter 1.5 h the reaction mixture was quenched by addition of saturated aq ammonium chloride
  2. concentrationThe solution was concentrated
  3. additionH2O was added
  4. washThe precipitate was washed with water and diethyl ether

Sources & evidence

ORD record
ord-00be1ff7b7d14de284cf8deedae7c1d4
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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