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 1157759Notes

Reaction equation

HRID 1157759 reaction equation
[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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-53209d94e8de4ccdb124ac6e58f7d54e
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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