Hydrochloric Acid → HCID 46893388, compound

HRID 1801955Notes

Reaction equation

HRID 1801955 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[O:9])[CH:5]=[CH:6][CH:7]=1.C1COCC1.CO.[BH4-].[Na+].Cl>CS(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[OH:9])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 21899815MeOH tetrahydrofuranHCID 46892241HCID 46892241, compound

Product 1

HCID 46893388HCID 46893388, compoundYield 33.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
0 °C

Procedure

To (3-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone from Example 1 (0.15 g, 0.43 mmol) in 1:1 THF/MeOH (4 mL) at 0° C. was added sodium borohydride (0.02 g, 0.58 mmol) and the mixture was stirred at 0° C. for 30 min. To the mixture were added 6 N HCl and DMSO (3 mL), and the mixture was purified by preparative HPLC (Varian diphenyl reverse phase column eluting with gradient of solvent B=0.05% HOAC/MeOH and solvent A=0.05% HOAc/H2O) to afford (3-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanol (50 mg, 32%). 1H NMR (300 MHz, DMSO-d6) δ 2.26 (s, 3H) 5.7 (s, 1H) 5.93 (s,1H) 6.44 (s, 1H) 7.07 (m, 1H) 7.34-7.39 (m, 3H) 7.54 (m, 1H) 7.81 (s, 2H) 8.59 (d, 1H) 10.42 (s, 1H) 12.15 (s, 1H); LC-MS (ESI) m/z 350 (M+H)+.

Workup

  1. customthe mixture was purified by preparative HPLC (Varian diphenyl reverse phase column
  2. washeluting with gradient of solvent B=0.05% HOAC/MeOH and solvent A=0.05% HOAc/H2O)

Sources & evidence

ORD record
ord-9dbda45dcc3f4db5a889144043f62d61
Source dataset
uspto-grants-2013_01
Patent number
US08349851B2

Reaction notes

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