Hydrochloric Acid → 3-[4-methoxy-3-[2-oxo-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]acetyl]-1H-pyrrolo[2,3-c]pyridin-7-yl]-1H-pyrazole-5-carboxylic acid

HRID 1157759ノート

反応式

HRID 1157759 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:13]=[C:12]([C:14]([O:16]CC)=[O:15])[NH:11][N:10]=2)=[C:5]2[NH:19][CH:20]=[C:21]([C:22](=[O:42])[C:23](=[O:41])[N:24]3[CH2:29][CH2:28][N:27]([C:30]4[N:34]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[N:33]=[N:32][N:31]=4)[CH2:26][CH2:25]3)[C:4]=12.O[Li].O.Cl>CN(C=O)C.O>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:13]=[C:12]([C:14]([OH:16])=[O:15])[NH:11][N:10]=2)=[C:5]2[NH:19][CH:20]=[C:21]([C:22](=[O:42])[C:23](=[O:41])[N:24]3[CH2:25][CH2:26][N:27]([C:30]4[N:34]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[N:33]=[N:32][N:31]=4)[CH2:28][CH2:29]3)[C:4]=12

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 24875208ethyl 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate

生成物 1

HCID 248747543-[4-methoxy-3-[2-oxo-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]acetyl]-1H-pyrrolo[2,3-c]pyridin-7-yl]-1H-pyrazole-5-carboxylic acid

試薬・触媒・溶媒 2

HCID 962Water溶媒3 回HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

To a suspension of ethyl 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate (0.124 g, 0.217 mmol) in DMF (1.5 mL) and H2O (1.5 mL) was added LiOH monohydrate (0.027 g, 0.651 mmol). The mixture was heated to 120° C. for 24 h. The reaction was not complete, so an additional 0.05 g of LiOH hydrate along with 2 mL of H2O were added to the mixture, and it was again heated to 120° C. After 24 h of heating, the reaction was nearly complete by LCMS, so it was cooled to rt, and made acidic (pH=1) with 6N HCl. The mixture was diluted with H2O, and partitioned with EtOAc. The product precipitated from between the two layers, and was collected by filtration. The solids were washed with cold MeOH and H2O. The 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylic acid (0.08 g) was collected as a light yellow solid. LCMS: m/e 542.97 (M+H)+, ret time 1.86 min (method 2). 1H NMR (500 MHz, DMSO-D6) δ ppm 12.10-12.22 (s, 1H) 8.25 (s, 1H) 8.10 (s, 1H) 7.56-7.77 (m, 5H) 7.39 (s, 1H) 3.99 (s, 3H) 3.67-3.72 (m, 2H) 3.40-3.46 (m, 2H) 3.29-3.36 (m, 2H) 3.14-3.20 (m, 2H).

後処理

  1. temperaturewas again heated to 120° C
  2. temperatureAfter 24 h of heating
  3. temperaturewas cooled to rt
  4. custompartitioned with EtOAc
  5. customThe product precipitated from between the two layers
  6. filtrationwas collected by filtration
  7. washThe solids were washed with cold MeOH and H2O
  8. customThe 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylic acid (0.08 g) was collected as a light yellow solid
  9. customm/e 542.97 (M+H)+, ret time 1.86 min (method 2)

出典と根拠

ORDレコード
ord-53209d94e8de4ccdb124ac6e58f7d54e
出典データセット
uspto-grants-2010_10
特許番号
US07807676B2

反応ノート

読み込み中…