Methanol → HCID 69811588, compound

HRID 1809454Notes

Reaction equation

HRID 1809454 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17](OC)=O)[N:12]3[C:21]=2[CH2:22][CH:23]=O)=[CH:5][CH:4]=1)#[N:2].[CH3:25][O:26][C:27]1[CH:34]=[C:33]([O:35][CH3:36])[CH:32]=[CH:31][C:28]=1[CH2:29][NH2:30].[BH3-]C#N.[Na+].C[OH:42]>>[CH3:25][O:26][C:27]1[CH:34]=[C:33]([O:35][CH3:36])[CH:32]=[CH:31][C:28]=1[CH2:29][N:30]1[CH:11]2[N:12]3[C:21](=[C:9]([C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=4)[N:10]=[CH:17][C:13]3=[CH:14][CH2:15][C:16]1=[O:42])[CH2:22][CH2:23]2

Participants

5

Reactant 4

HCID 887MethanolHCID 5972502,4-DimethoxybenzylamineHCID 5003444Sodium cyanoborohydrideHCID 86651535HCID 86651535, compound

Product 1

HCID 69811588HCID 69811588, compound

Procedure

To a solution of methyl 2-(4-cyanophenyl)-3-(2-oxoethyl)imidazo[1,2-a]pyridine-5-carboxylate in MeOH (0.2 M), 2,4-dimethoxybenzylamine (1.2 eq.) was added and the reaction mixture was stirred at RT for 2 h. Then, NaBH3CN (1.5 eq.) was added and stirring was continued for 12 h. The solvent was reduced in vacuo and the residue partitioned between sat. aq. NaHCO3 and DCM. The aqueous phase was separated and extracted several times with DCM. The combined organic extracts were washed with brine and dried (Na2SO4). Evaporation of the solvent gave a residue which was purified by flash column on silica using a gradient of EtOAc/Petroleum ether from 30:70 to 50:50 to yield (55% over two steps) the title compound. 1H NMR (600 MHz, DMSO-d6, 330K) δ 7.96 (2H, d, J=8.4 Hz), 7.93 (2H, d, J=8.4 Hz), 7.85 (1H, d, J=8.8 Hz), 7.80 (1H, d, J=7.0 Hz), 7.45 (1H; dd, J=9.0, 7.0 Hz), 7.22 (1H, d, J=8.0 Hz), 6.62 (1H, d, J=2 Hz), 6.53 (1H; dd, J=8.4, 2.0 Hz), 4.73 (2H; s), 3.84 (3H, s), 3.77 (3H, s), 3.72-3.68 (2H, m), 3.46-3.42 (2H, m). MS (ES+C26H22N4O3 requires: 438, found: 439 (M+H)+.

Workup

  1. stirringstirring
  2. waitwas continued for 12 h
  3. customthe residue partitioned between sat. aq. NaHCO3 and DCM
  4. customThe aqueous phase was separated
  5. extractionextracted several times with DCM
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. customEvaporation of the solvent
  9. customgave a residue which
  10. customwas purified by flash column on silica using a gradient of EtOAc/Petroleum ether from 30:70 to 50:50

Sources & evidence

ORD record
ord-c4896fabe1b44846b8e9ee83c4dbeaee
Source dataset
uspto-grants-2013_01
Patent number
US08362030B2

Reaction notes

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