Hydrochloric Acid → (R)-isopropyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate hydrochloride

HRID 1693032Notes

Reaction equation

HRID 1693032 reaction equation
[ClH:1].CCOCC.[OH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[N:23]=[C:22]([N:24]2[CH2:28][CH2:27][C@@H:26]([NH:29][C:30](=[O:35])[O:31][CH:32]([CH3:34])[CH3:33])[CH2:25]2)[C:21]2[C:16](=[CH:17][C:18]([CH3:36])=[CH:19][CH:20]=2)[N:15]=1>C(Cl)Cl.CO>[ClH:1].[OH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[N:23]=[C:22]([N:24]2[CH2:28][CH2:27][C@@H:26]([NH:29][C:30](=[O:35])[O:31][CH:32]([CH3:33])[CH3:34])[CH2:25]2)[C:21]2[C:16](=[CH:17][C:18]([CH3:36])=[CH:19][CH:20]=2)[N:15]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl Ether2×HCID 135771842(R)-isopropyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate

Product 1

HCID 136406835(R)-isopropyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate hydrochlorideYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Under an N2 atmosphere, a 2.0 M HCl solution in ether (0.30 mL, 0.60 mmol) was added to a solution of (R)-isopropyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (246 mg, 0.6 mmol) in a mixture of CH2Cl2 (10 mL) and MeOH (1 mL). After the addition of ether (15 mL), a precipitate formed, and the mixture was stirred for an additional 20 minutes. The solid was collected by vacuum filtration and dried to obtain (R)-isopropyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate hydrochloride (HCl salt of compound 12) (215 mg, 80%). 1H NMR (400 MHz, DMSO-d6) δ 8.22 (d, J=8.1 Hz, 1H), 8.14 (dd, J=7.9, 1.4 Hz, 1H), 7.69 (s, 1H), 7.54-7.48 (m, 2H), 7.08-7.03 (m, 2H), 4.77-4.71 (m, 1H), 4.25-4.12 (m, 4H), 3.93-3.91 (m, 1H), 2.50 (s, 3H), 2.25-2.23 (m, 1H), 2.06-2.03 (m, 1H), 1.16-1.12 (m, 6H) ppm. LC/MS: m/z 407.5 (M+H)+ at 2.43 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customa precipitate formed
  2. filtrationThe solid was collected by vacuum filtration
  3. customdried

Sources & evidence

ORD record
ord-172dec7106e4474eb04a48235218fca2
Source dataset
uspto-grants-2012_04
Patent number
US08158637B2

Reaction notes

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