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 1157759노트

반응식

HRID 1157759 반응식
[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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 2

HCID 962Water용매3회HCID 6228Dimethylformamide용매

반응 조건

온도
120 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-53209d94e8de4ccdb124ac6e58f7d54e
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807676B2

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