Pyrrolidine → 5-methyl-3-{1-[4-(pyrrolidin-1-ylmethyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole

HRID 1520049Notes

Reaction equation

HRID 1520049 reaction equation
C([BH3-])#N.[Na+].[CH3:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[C:15]1[N:16]=[N:17][N:18]([C:20]2[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=2)[CH:19]=1.[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1.[BH4-].[Na+]>CC(N(C)C)=O>[CH3:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[C:15]1[N:16]=[N:17][N:18]([C:20]2[CH:27]=[CH:26][C:23]([CH2:24][N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:22][CH:21]=2)[CH:19]=1

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 4311764Sodium borohydrideHCID 5003444Sodium cyanoborohydrideHCID 715340964-[4-(5-methyl-1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzaldehyde

Product 1

HCID 680609195-methyl-3-{1-[4-(pyrrolidin-1-ylmethyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Sodium cyanoborohydride (166 mg; 2.64 mmol; 4.0 eq.) was added to a solution of 4-[4-(5-methyl-1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzaldehyde (200 mg; 0.66 mmol; 1.0 eq.) and pyrrolidine (1.64 mL; 19.8 mmol; 30 eq.) in DMA (4 mL) and the reaction mixture was stirred at RT. After 12 h, as no product was detected, sodium borohydride was added (100 mg; 2.64 mmol; 4.0 eq.) and the reaction mixture was stirred at RT for 1 hour. Reaction was quenched with water and extracted with EtOAc (twice). Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by preparative HPLC afforded the title compound as a formic acid salt. It was dissolved in MeOH and passed through a SPE-NH2 cartridge. The fractions containing the desired compound were concentrated to dryness affording a yellow gum, which was twice sonicated in 3 mL of Et2O. The suspension obtained was concentrated then dried overnight under high vacuum to afford the title compound as a beige solid. 1H NMR (300 Mz, DMSO-d6) δ: 13.245 (brs, 1H), 9.26 (s, 1H), 8.14-8.13 (m, 1H), 7.99 (d, J=8.5 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.5 Hz, 1H), 7.27 (dd, J=8.5 Hz, 1.5 Hz, 1H), 3.67 (s, 2H), 2.49-2.45 (m, 7H), 1.74-1.70 (m, 4H). HPLC (Condition A): Rt 2.63 min (purity 99.5%). MS (ESI+): 359.2, MS (ESI−): 357.3.

Workup

  1. stirringthe reaction mixture was stirred at RT for 1 hour
  2. customReaction
  3. customwas quenched with water
  4. extractionextracted with EtOAc (twice)
  5. washCombined organic phases were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-78fbfb7406a84d8a9380a508d372e65d
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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