Acetic Acid → HCID 70945244, compound

HRID 518013Notes

Reaction equation

HRID 518013 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH:19]=O)=[C:13]([C:21]([F:24])([F:23])[F:22])[CH:12]=3)[N:7]=[C:6]([C:25]#[N:26])[C:5]=2[N:4]=[N:3]1.[C@H:27]12[CH2:33][C@H:30]([NH:31][CH2:32]1)[CH2:29][N:28]2[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO.C(OCC)(=O)C>[C:25]([C:6]1[C:5]2[N:4]=[N:3][N:2]([CH3:1])[C:10]=2[CH:9]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][N:31]3[CH2:32][C@@H:27]4[CH2:33][C@H:30]3[CH2:29][N:28]4[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[C:13]([C:21]([F:24])([F:23])[F:22])[CH:12]=2)[N:7]=1)#[N:26]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 86673358HCID 86673358, compound

Product 1

HCID 70945244HCID 70945244, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl-6-(4-(3-oxopropyl)-3-(trifluoromethyl)phenyl)-1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile (200 mg), (1S,4S)-tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (221 mg) was dissolved in a mixed solvent of DCM (3 ml) and methanol (5 ml) containing acetic acid (0.4 ml). Sodium triacetoxyborohydride (350 mg) was then added in portions and the mixture was stirred at rt for further 3 hours. After diluting with ethyl acetate (100 ml), washed with sodium carbonate (30 ml), brine (20 ml), dried over sodium sulphate, solvent removed under vacuum, residue was then columned on silica gel using DCM:MeOH (20:1) as eluant to give (1S,4S)-tert-butyl 5-(3-(4-(4-cyano-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)-2-(trifluoro-methyl)phenyl)propyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (220 mg). 1H NMR (CDCl3) δ: 8.33 (s, 1H), 8.26 (d, 1H), 8.04 (s, 1H), 7.55 (d, 1H), 4.46 (s, 3H), 4.40 (br, 0.4H), 4.25 (br, 0.6H), 3.4-3.6 (m, 2H), 3.18 (m, 1H), 2.8-3.0 (m, 3H), 2.5-2.75 (m, 3H), 1.5-1.9 (m, 4H), 1.46 (s, 9H). MS m/z 542 (M+H).

Workup

  1. washwashed with sodium carbonate (30 ml), brine (20 ml)
  2. dry with materialdried over sodium sulphate, solvent
  3. customremoved under vacuum, residue

Sources & evidence

ORD record
ord-bf585c3c505c4507aedbc877b75949a3
Source dataset
uspto-grants-2015_08
Patent number
US09115126B2

Reaction notes

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