HCID 178418676, compound → HCID 178488739, compound

HRID 1801918Notes

Reaction equation

HRID 1801918 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, 3 H) 6.75 (s, 1 H) 7.35-7.41 (m, 3 H) 7.58-7.65 (m, 2 H) 8.07-8.12 (m, 2 H) 8.2 (d, J=8.48 Hz, 1 H) 10.64 (br. s., 1 H) 12.51 (br. s., 1 H) 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 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, 3 H) 6.75 (s, 1 H) 7.35-7.41 (m, 3 H) 7.58-7.65 (m, 2 H) 8.07-8.12 (m, 2 H) 8.2 (d, J=8.48 Hz, 1 H) 10.64 (br. s., 1 H) 12.51 (br. s., 1 H) LC-MS (ESI) m/z 364 (M+H)+

Sources & evidence

ORD record
ord-06689e308bf746c691b139f5e8893342
Source dataset
uspto-grants-2013_01
Patent number
US08349851B2

Reaction notes

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