Hydrochloric Acid → HCID 58864337、化合物

HRID 1353514ノート

反応式

HRID 1353514 の反応式
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

参加物

7

反応物 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 58864519HCID 58864519、化合物

生成物 1

HCID 58864337HCID 58864337、化合物収率 90.2%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-dbf8519250954a31b925cdc4db51bc57
出典データセット
uspto-grants-2007_05
特許番号
US07220862B2

反応ノート

読み込み中…