Hydrochloric Acid → HCID 58864337, 화합물

HRID 1177686노트

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HRID 1177686 반응식
C[O:2][C:3](=[O:44])[C@H:4]([NH:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([N:33]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[NH:35][C:34]2=[O:43])[CH2:29][CH2:28]1)=[O:26])[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([S:15]([CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])(=[O:17])=[O:16])[N:10]=[CH:9]2.O.[OH-].[Li+].Cl>O1CCCC1.CO.O>[O:43]=[C:34]1[N:33]([CH:30]2[CH2:29][CH2:28][N:27]([C:25]([NH:24][C@H:4]([CH2:5][C:6]3[CH:7]=[C:8]4[C:12](=[CH:13][CH:14]=3)[N:11]([S:15]([CH2:18][CH2:19][Si:20]([CH3:21])([CH3:23])[CH3:22])(=[O:17])=[O:16])[N:10]=[CH:9]4)[C:3]([OH:44])=[O:2])=[O:26])[CH2:32][CH2:31]2)[CH2:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35]1

참가 물질

7

반응물 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 58864519HCID 58864519, 화합물

생성물 1

HCID 58864337HCID 58864337, 화합물수율 90.2%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

A solution of (R)-2-{[4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-3-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indazol-5-yl]-propionic acid methyl ester (775 mg, 1.21 mmol) in tetrahydrofuran (9 mL) and methanol (3 mL) was cooled to 0° C. A solution of lithium hydroxide monohydrate (115 mg, 4.84 mmol) in water (3 mL) was added. The reaction mixture was stirred at 0° C. for 2 h and then placed in the freezer at −15° C. for 16 h. While cooling the reaction mixture with an ice bath, the pH was increased to ca. 7 by addition of 1N hydrochloric acid (3.8 mL). Organic solvents were removed under vacuum. The resulting aqueous solution was extracted with ethyl acetate after additon of more 1N hydrochloric acid (0.5 mL). The combined extracts were dried over magnesium sulfate, filtered and evaporated to give 684 mg (90%) of the title compound as a white solid. 1H-NMR (DMSO-d6, 300 MHz) δ 9.21 (s, 1H), 8.58 (s, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.78 (s, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.13-7.09 (m, 2H), 6.88-6.83 (m, 1H), 6.76-6.74 (m, 2H), 4.33-4.27 (m, 2H), 4.18 (s, 2H), 4.09-3.96 (m, 3H), 3.57-3.51 (m, 2H), 3.25-3.04 (m, 2H), 2.74-2.60 (m, 2H), 1.54-1.43 (m, 4H), 0.70-0.64 (m, 2H), −0.08 (s, 9H). Mass spec.: 627 (MH)+.

후처리

  1. waitplaced in the freezer at −15° C. for 16 h
  2. temperatureWhile cooling the reaction mixture with an ice bath
  3. customOrganic solvents were removed under vacuum
  4. extractionThe resulting aqueous solution was extracted with ethyl acetate after additon of more 1N hydrochloric acid (0.5 mL)
  5. dry with materialThe combined extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated

출처 및 근거

ORD 기록
ord-21437ab417c14aa88bbbe1a649a33355
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842808B2

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