2-Fluoro-6-methoxybenzaldehyde → (R)-5-(5-(1-(2-fluoro-6-methoxybenzyl)piperidin-3-yl)-1-methyl-1H-1,2,4-triazol-3-yl)-3-(pyridin-4-yl)-1H-indazole

HRID 1465707Notes

Reaction equation

HRID 1465707 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH3:11])[C:3]=1[CH:4]=O.[CH3:12][N:13]1[C:17]([C@@H:18]2[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]2)=[N:16][C:15]([C:24]2[CH:25]=[C:26]3[C:30](=[CH:31][CH:32]=2)[NH:29][N:28]=[C:27]3[C:33]2[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=2)=[N:14]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C(Cl)Cl.O>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH3:11])[C:3]=1[CH2:4][N:20]1[CH2:21][CH2:22][CH2:23][C@@H:18]([C:17]2[N:13]([CH3:12])[N:14]=[C:15]([C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[NH:29][N:28]=[C:27]4[C:33]3[CH:34]=[CH:35][N:36]=[CH:37][CH:38]=3)[N:16]=2)[CH2:19]1

Participants

7

Reactant 3

HCID 27373572-Fluoro-6-methoxybenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86695582(R)-5-(1-methyl-5-(piperidin-3-yl)-1H-1,2,4-triazol-3-yl)-3-(pyridin-4-yl)-1H-indazole

Product 1

HCID 56971413(R)-5-(5-(1-(2-fluoro-6-methoxybenzyl)piperidin-3-yl)-1-methyl-1H-1,2,4-triazol-3-yl)-3-(pyridin-4-yl)-1H-indazoleYield 63.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Added 2-Fluoro-6-methoxy benzaldehyde (20 mg, 0.129 mmol) to a solution of (R)-5-(1-methyl-5-(piperidin-3-yl)-1H-1,2,4-triazol-3-yl)-3-(pyridin-4-yl)-1H-indazole (15 mg, 0.0379 mmol) and sodium triacetoxyborohydride (25 mg, 0.118 mmol) in MeOH (4 ml) at room temperature, then stirred for 2 hours. Reaction was diluted with CH2Cl2 (50 ml) and H2O (25 ml), organic layer was separated, dried over Na2SO4, filtered and solvent evaporated. The residue was chromatographed on silica gel eluting with 5% v/v MeOH/CH2Cl2/NH4OH to yield (R)-5-(5-(1-(2-fluoro-6-methoxybenzyl)piperidin-3-yl)-1-methyl-1H-1,2,4-triazol-3-yl)-3-(pyridin-4-yl)-1H-indazole as a white solid (12 mg).

Workup

  1. customReaction
  2. customwas separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customsolvent evaporated
  6. customThe residue was chromatographed on silica gel eluting with 5% v/v MeOH/CH2Cl2/NH4OH

Sources & evidence

ORD record
ord-b48628639f43466bb4eb1c57bfb8aa56
Source dataset
uspto-grants-2015_04
Patent number
US08999966B2

Reaction notes

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