Hydrochloric Acid → (S)-tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate hydrochloride

HRID 2079362Notes

Reaction equation

HRID 2079362 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:17]=[C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([CH2:24][NH:25][C:26](=[O:33])[O:27][C@H:28]3[CH2:32][CH2:31][O:30][CH2:29]3)[CH2:19]2)[C:15]2[C:10](=[CH:11][C:12]([CH3:34])=[CH:13][CH:14]=2)[N:9]=1.[ClH:35]>C(Cl)Cl.CCOCC>[ClH:35].[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:17]=[C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([CH2:24][NH:25][C:26](=[O:33])[O:27][C@H:28]3[CH2:32][CH2:31][O:30][CH2:29]3)[CH2:19]2)[C:15]2[C:10](=[CH:11][C:12]([CH3:34])=[CH:13][CH:14]=2)[N:9]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 136121431(S)-Tetrahydrofuran-3-yl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

Product 1

HCID 136330116(S)-tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate hydrochlorideYield 86%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Procedure

(S)-Tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate (115 mg, 0.251 mmol) was suspended in 8 mL of anhydrous CH2Cl2 and gently heated until an homogenous solution was formed. After cooling to room temperature, a 2.0 M solution of HCl in Et2O (0.126 mL, 0.251 mmol) was added in one portion. The reaction mixture was diluted with 25 mL Et2O, and the product precipitated from the solution. The reaction was stirred for an additional 30 minutes before the solid was filtered and dried to obtain (S)-tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate hydrochloride (108 mg, 86%) as a light yellow solid. LC/MS: m/z 463.5 (M+H)+ at 2.37 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.18 (d, J=6.6 Hz, 1H), 7.94 (d, J=8.6 Hz, 1H), 7.73 (s, 1H), 7.44-7.51 (m, 2H), 7.00-7.07 (m, 2H), 5.06-5.09 (m, 1H), 4.52-4.62 (m, 2H), 3.62-3.74 (m, 4H), 3.23-3.29 (m, 1H), 3.00 (d, J=6.8 Hz, 2H), 2.52 (s, 3H), 2.02-2.11 (m, 1H), 1.61-2.01 (m, 4H), 1.24-1.43 (m, 2H), 0.84-0.89 (m, 1H) ppm.

Workup

  1. temperaturegently heated until an homogenous solution
  2. customwas formed
  3. customthe product precipitated from the solution
  4. filtrationwas filtered
  5. customdried

Sources & evidence

ORD record
ord-11a3091dc35e45f4bb950aeac808cc17
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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