Hydrochloric Acid → (R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one hydrochloride

HRID 2062197Notes

Reaction equation

HRID 2062197 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[C:9]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][N:22]([C:25](=[O:33])[C@H:26]([OH:32])[CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:21][CH2:20]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:34])=[CH:14][CH:15]=2)[N:10]=1.CCOCC.[ClH:40]>C(Cl)Cl>[ClH:40].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[C:9]1[N:18]=[C:17]([N:19]2[CH2:20][CH2:21][N:22]([C:25](=[O:33])[C@H:26]([OH:32])[CH2:27][C:28]([CH3:29])([CH3:30])[CH3:31])[CH2:23][CH2:24]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:34])=[CH:14][CH:15]=2)[N:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3283Diethyl Ether2×HCID 135438360HCID 135438360, compound

Product 1

HCID 136366706(R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one hydrochlorideYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-1-(4-(2-(2-Fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one (171 mg, 0.367 mmol) was dissolved in anhydrous CH2Cl2 (2 mL) followed by the addition of Et2O (6 ml) under an N2 atmosphere. A 2.0 M HCl solution in Et2O (0.184 mL, 0.367 mmol) was added over a 1 minute period. The reaction solution changed from a clear yellow solution to a milky white slurry. After complete addition of the HCl solution, the reaction was allowed to stir for an additional 10 minutes. The product was collected by vacuum filtration and dried under vacuum to obtain (R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one hydrochloride as a light yellow solid (170 mg, 92%). LC/MS: m/z 467.3 (M+H)+ at 2.60 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J=8.3 Hz, 1H), 7.66 (s, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.48-7.43 (m, 1H), 6.92-6.83 (m, 2H), 4.44-4.41 (m, 1H), 3.87-3.68 (m, 8H), 2.56 (s, 3H), 1.55 (dd, J=14.3, 3.0 Hz, 1H), 1.41 (dd, J=14.3, 8.8 Hz, 1H), 0.96 (s, 9H).

Workup

  1. filtrationThe product was collected by vacuum filtration
  2. customdried under vacuum

Sources & evidence

ORD record
ord-b3da265de80340f28cabf5f20bd79033
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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