HCID 59511221, compound → 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

HRID 1157287Notes

Reaction equation

HRID 1157287 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]2[C:10]([C:11](=[O:31])[C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.C([Sn](CCCC)(CCCC)[C:39]1[CH:43]=[C:42]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[NH:41][N:40]=1)CCC>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:33][O:32][C:5]1[CH:4]=[N:3][C:2]([C:39]2[CH:43]=[C:42]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[NH:41][N:40]=2)=[C:7]2[NH:8][CH:9]=[C:10]([C:11](=[O:31])[C:12](=[O:13])[N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)[C:6]=12

Participants

5

Reactant 2

HCID 59511221HCID 59511221, compoundHCID 178448219HCID 178448219, compound

Product 1

HCID 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

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of 1-(7-chloro-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (2.50 g, 5.35 mmol) in 1,4-dioxane (60 mL) in a sealable flask was added ethyl 3-(tributylstannyl)-1H-pyrazole-5-carboxylate (2.30 g, 5.36 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (1.86 g, 1.61 mmol). The mixture was flushed with N2, the flask was sealed, and the mixture was heated to 120° C. for 16 hr. The mixture was cooled to rt and diluted with MeOH (50 mL). The remaining solids were removed by filtering the mixture through a pad of celite and were washed with MeOH (25 mL). The remaining solvent was concentrated under reduced pressure. The resulting residue was dissolved in MeOH, and loaded onto a silica gel. After the silica was dry, a column was run using the biotage system with a 0 to 10% MeOH in CH2Cl2 gradient. After concentrating the desired fractions, 1.05 g 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 was recovered as an orange solid. LCMS: m/e 571.2 (M+H)+, ret time 2.01 min (method 2). 1H NMR (500 MHz, DMSO-D6) δ ppm 12.39-12.72 (m, 1 H) 8.37 (s, 1 H) 8.11 (s, 1 H) 7.52-7.76 (m, 6 H) 4.68-4.85 (m, 1 H) 4.38 (q, J=7.02 Hz, 2 H) 3.98-4.06 (m, 3 H) 3.67-3.73 (m, 2 H) 3.43-3.49 (m, 2 H) 3.28-3.36 (m, 2 H) 3.14-3.22 (m, 2 H) 1.36 (t, J=7.17 Hz, 3 H).

Workup

  1. customThe mixture was flushed with N2
  2. customthe flask was sealed
  3. temperatureThe mixture was cooled to rt
  4. additiondiluted with MeOH (50 mL)
  5. customThe remaining solids were removed
  6. filtrationby filtering the mixture through a pad of celite
  7. washwere washed with MeOH (25 mL)
  8. concentrationThe remaining solvent was concentrated under reduced pressure
  9. dissolutionThe resulting residue was dissolved in MeOH
  10. customAfter the silica was dry
  11. concentrationAfter concentrating the desired fractions, 1.05 g 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
  12. customwas recovered as an orange solid
  13. customm/e 571.2 (M+H)+, ret time 2.01 min (method 2)

Sources & evidence

ORD record
ord-42b2500a38004741bd0714634df89ac9
Source dataset
uspto-grants-2010_10
Patent number
US07807671B2

Reaction notes

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