Hydrochloric Acid → HCID 49770049, compound

HRID 1157802Notes

Reaction equation

HRID 1157802 reaction equation
[C:1]1([N:7]2[C:11]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20]C(C)(C)C)=O)[CH2:14][CH2:13]3)=[N:10][N:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[F:26][C:27]1[CH:32]=[N:31][C:30]([N:33]2[CH:37]=[CH:36][N:35]=[N:34]2)=[C:29]2[NH:38][CH:39]=[C:40]([C:41](=[O:45])C(O)=O)[C:28]=12.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>O1CCOCC1>[F:26][C:27]1[CH:32]=[N:31][C:30]([N:33]2[CH:37]=[CH:36][N:35]=[N:34]2)=[C:29]2[NH:38][CH:39]=[C:40]([C:41](=[O:45])[C:18]([N:15]3[CH2:14][CH2:13][CH:12]([C:11]4[N:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[N:8]=[N:9][N:10]=4)[CH2:17][CH2:16]3)=[O:20])[C:28]=12

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58806128HCID 58806128, compoundHCID 68690008HCID 68690008, compound

Product 1

HCID 49770049HCID 49770049, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
25 °C

Procedure

Part C: To a solution of tert-butyl 4-(1-phenyl-1H-tetrazol-5-yl)piperidine-1-carboxylate (0.165 g, 0.50 mmol) in 1,4-dioxane (10 mL) at 25° C. was added 4.00 N HCl in 1,4-dioxane (10 mL), and the mixture was stirred at 25° C. for 16 h. The mixture then was concentrated under vacuum. The resulting solids were dissolved in DMF (10 mL). To this solution was added sequentially 2-(4-fluoro-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (0.137 g, 0.50 mmol), N-methylmorpholine (0.165 mL, 1.50 mmol), and TBTU (0.176 g, 0.55 mmol), and the mixture was stirred at 25° C. for 24 h. The reaction mixture was filtered, and the filtrate was concentrated under vacuum. The residue was dissolved in hot methanol, and the solution then was allowed to cool slowly to room temperature. The precipitate was recovered by filtration, washed with methanol, and dried under vacuum to provide 1-(4-fluoro-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperidin-1-yl)ethane-1,2-dione (0.142 g) as an off-white solid; mp: 257-258° C.; HRMS: 487.1740 (M+H)+ [calc'd: 487.1755]; 1H NMR (500 MHz, DMSO-D6) δ 13.06 (br s, 1H), 9.02 (s, 1H), 8.32 (d, 1H, J=1.8 Hz), 8.30 (s, 1H), 8.12 (s, 1H), 7.58 (s, 5H), 4.37 (m, 1H), 3.67 (m, 1H), 3.32 (m, 1H), 3.25 (m, 1H), 3.03 (m, 1H), 2.01 (m, 1H), 1.88 (m, 1H), 1.83-1.70 (m, 2H).

Workup

  1. concentrationThe mixture then was concentrated under vacuum
  2. dissolutionThe resulting solids were dissolved in DMF (10 mL)
  3. stirringthe mixture was stirred at 25° C. for 24 h
  4. filtrationThe reaction mixture was filtered
  5. concentrationthe filtrate was concentrated under vacuum
  6. dissolutionThe residue was dissolved in hot methanol
  7. temperatureto cool slowly to room temperature
  8. filtrationThe precipitate was recovered by filtration
  9. washwashed with methanol
  10. customdried under vacuum

Sources & evidence

ORD record
ord-204f2d0c0af945dea456988541af18d4
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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