Hydrochloric Acid → (S)-(4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol hydrochloride

HRID 2369256Notes

Reaction equation

HRID 2369256 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H: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:4][CH:3]=1.[ClH:27]>CC#N.O>[ClH:27].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H: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:4][CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 56833308(S)-(4-Fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol

Product 1

HCID 66617204(S)-(4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol hydrochlorideYield 102.5%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a suspension of (S)-(4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol (4.33 g) in 1:1 CH3CN/H2O (100 mL) was added 1N HCl (15.5 mL, 15.5 mmol). The solution was frozen and lyophilized to afford 4.9 g of (S)-(4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol hydrochloride as a solid. 1H NMR (300 MHz, DMSO-d6) δ 14.61 (br s., 1H), 12.16 (br s., 1H), 8.84 (d, J=8.1 Hz, 1H), 8.24 (d, J=8.1 Hz, 1H), 8.02-8.13 (m, 1H), 7.73-7.88 (m, 1H), 7.55-7.70 (m, 2H), 7.18-7.36 (m, 2H), 6.21 (s, 1H), 6.02 (s, 1H), 3.93 (br s, 2H, obscured by H2O peak), 2.26 (s, 3H); LC-MS (ESI) m/z: 350 (M+H)+. Analysis by chiral HPLC showed that the HCl salt had an enantiomeric excess of about 100%.

Workup

  1. temperatureThe solution was frozen

Sources & evidence

ORD record
ord-7b9adf8ccaba4ae5ab77572d0256dbe4
Source dataset
uspto-grants-2014_04
Patent number
US08703943B2

Reaction notes

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