Ammonium formate → 1-Piperidinecarboxylic acid, 4-[4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl]-, 1,1-dimethylethyl ester

HRID 1520076Notes

Reaction equation

HRID 1520076 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[N:11]=[N:12][N:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH:26]=4)=[CH:17][CH:16]=3)[CH:14]=2)=[N:2]1.C([O-])=O.[NH4+]>C1COCC1.[Pd]>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[N:11]=[N:12][N:13]([C:15]3[CH:16]=[CH:17][C:18]([CH:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]4)=[CH:19][CH:20]=3)[CH:14]=2)=[N:2]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 67981119HCID 67981119, compound

Product 1

HCID 679810931-Piperidinecarboxylic acid, 4-[4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl]-, 1,1-dimethylethyl esterYield 94.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

In a Parr reactor, Pd/C (10% Pd moistened, 50% water, 24 mg, 0.23 mmol, 0.1 eq.) was suspended in a solution of tert-butyl 4-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate (1.0 g; 2.26 mmol; 1.0 eq.) and ammonium formate (2.85 g; 45.2 mmol; 20 eq.) in THF (55 mL). The reaction mixture was stirred for 48 h at 70° C. It was then filtered through a celite pad, the cake was rinsed several times with THF and the filtrate was concentrated to dryness. The resulting residue was partitioned between DCM and water. Organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM:MeOH, gradient from 100:0 to 95:5) gave the title compound as a white foam (950 mg g; 94.5%). 1H NMR (300 MHz, DMSO-d6) δ 13.36 (brs, 1H), 9.27 (s, 1H), 8.36 (d, J=8.2 Hz, 1H), 8.01-7.93 (m, 2H), 7.61 (d, J=8.4 Hz, 1H), 7.56-7.39 (m, 3H), 7.30-7.20 (m, 1H), 4.27-3.94 (m, 2H), 3.01-2.63 (m, 3H), 1.96-1.70 (m, 2H), 1.69-1.47 (m, 2H), 1.43 (s, 9H). 1H HPLC (max plot) 97.2%; Rt 5.33 min. UPLC/MS: (MS+) 445.2, (MS−) 443.2.

Workup

  1. filtrationIt was then filtered through a celite pad
  2. washthe cake was rinsed several times with THF
  3. concentrationthe filtrate was concentrated to dryness
  4. customThe resulting residue was partitioned between DCM and water
  5. washOrganic phase was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by flash chromatography on silica (DCM:MeOH, gradient from 100:0 to 95:5)

Sources & evidence

ORD record
ord-1782e6cf51a4461a9da69c3a056a2ef2
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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