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

HRID 2079356
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HRID 2079356 반응식
[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
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참가 물질

5

반응물 2

HCID 313Hydrochloric AcidHCID 136121430(R)-Tetrahydrofuran-3-yl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

생성물 1

HCID 136330115(R)-tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate hydrochloride수율 70%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매2회
HCID 6344
Dichloromethane
용매

실험 절차

(R)-Tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate (116 mg, 0.251 mmol) was suspended in 8 mL anhydrous CH2Cl2 and gently heated until an homogenous solution was formed. After the reaction was cooled 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 solution. The reaction was stirred for an additional 30 minutes before the solid was filtered and dried to obtain (R)-tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate hydrochloride as a light yellow solid (99 mg, 70%). 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 8.22 (d, J=7.7 Hz, 1H), 7.95 (d, J=8.5 Hz, 1H), 7.75 (s, 1H), 7.42-7.49 (m, 3H), 6.97-7.08 (m, 2H), 5.08 (dd, J=6.1, 4.6 Hz, 1H), 4.52-4.54 (m, 2H), 3.66-3.78 (m, 3H), 3.58-3.60 (m, 1H), 3.48 (t, J=10.7 Hz, 1H), 3.23 (t, J=11.5 Hz, 1H), 3.00 (t, J=6.3 Hz, 2H), 2.53 (s, 3H), 2.05-2.14 (m, 1H), 1.80-1.91 (m, 4H), 1.72 (d, J=9.0 Hz, 1H), 1.34-1.43 (m, 1H) ppm.

후처리

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

출처 및 근거

ORD 기록
ord-c95fbeedf7d140a59114420509023492
출처 데이터셋
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07928107B2

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