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

HRID 2079232Notes

Reaction equation

HRID 2079232 reaction equation
[OH:1][C@H:2]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[C:20]3[C:15](=[CH:16][C:17]([CH3:21])=[CH:18][CH:19]=3)[N:14]=[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[OH:28])[N:12]=2)[CH2:7][CH2:6]1)=[O:4].CCOCC.[ClH:39]>C(Cl)Cl>[ClH:39].[OH:1][C@H:2]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[C:20]3[C:15](=[CH:16][C:17]([CH3:21])=[CH:18][CH:19]=3)[N:14]=[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[OH:28])[N:12]=2)[CH2:7][CH2:6]1)=[O:4]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3283Diethyl Ether2×HCID 135491772(R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4,4-dimethylpentan-1-one

Product 1

HCID 136366918(R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4,4-dimethylpentan-1-one hydrochlorideYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-2-Hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4,4-dimethylpentan-1-one (265 mg, 0.367 mmol) was dissolved in anhydrous CH2Cl2 (3 mL) followed by the addition of Et2O (6 mL) under an N2 atmosphere. A 2.0 M HCl solution in Et2O (0.296 mL, 0.591 mmol) was added over a 1 minute period. The reaction solution changed from a clear yellow solution to a creamy off 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, washed with 3 mL of Et2O and dried under vacuum to obtain (R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4,4-dimethylpentan-1-one hydrochloride as a white solid (261 mg, 91%). LC/MS: m/z 449.3 (M+H)+ at 2.79 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J=7.6 Hz, 1H), 8.07 (d, J=8.6 Hz, 1H), 7.75 (s, 1H), 7.47-7.43 (m, 2H), 7.04-6.98 (m, 2H), 4.47-4.44 (m, 1H), 4.13-4.04 (m, 4H), 3.91-3.68 (m, 4H), 2.54 (s, 3H), 1.57 (dd, J=14.3, 3.1 Hz, 1H), 1.42 (dd, J=14.3, 8.8 Hz, 1H), 0.97 (s, 9H) ppm.

Workup

  1. filtrationThe product was collected by vacuum filtration
  2. washwashed with 3 mL of Et2O
  3. customdried under vacuum

Sources & evidence

ORD record
ord-d9aa6cbed37c4db180986dc51153ead5
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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