Cyano-borohydride → HCID 118195057, compound

HRID 1048702Notes

Reaction equation

HRID 1048702 reaction equation
C([BH3-])#N.[F:4][C:5]([F:26])([F:25])[C:6]1[CH:7]=[C:8]([C:12]#[C:13][C:14]2[N:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]3=[N:16][C:15]=2[CH2:23][NH2:24])[CH:9]=[CH:10][CH:11]=1.O.O=[CH:29][C:30]([OH:32])=[O:31]>ClCCl.CO>[F:26][C:5]([F:4])([F:25])[C:6]1[CH:7]=[C:8]([C:12]#[C:13][C:14]2[N:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]3=[N:16][C:15]=2[CH2:23][NH:24][CH2:29][C:30]([OH:32])=[O:31])[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 3

HCID 498716Cyano-borohydrideHCID 15620607Glyoxylic acid, monohydrateHCID 90024362HCID 90024362, compound

Product 1

HCID 118195057HCID 118195057, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

In a reactor equipped with a filter and an emptying system and placed on a vortex, were introduced 0.33 g (0.656 mmol) of cyanoborohydride resin. The resin was swelled in 3 ml of dichloromethane, the mixture was stirred at r.t. for 10 min and then dichloromethane was removed by filtration. The operation was repeated a second time and then a mixture of 0.2 g of (3-((3-(trifluoromethyl)phenyl)ethynyl) imidazo[1,2-a]pyridin-2-yl) methanamine and 0.055 g (0.596 mmol) of 2-oxoacetic acid hydrate solubilised in 3 ml of methanol was added. The mixture was stirred under a slow vortex at r.t. for 24 h. The resin was removed by filtration, washed with 15 ml of methanol, 15 ml of dichloromethane and then again 15 ml of methanol. The obtained filtrate was concentrated in vacuo and the residue was purified by flash chromatography on a silica gel cartridge (eluent: dichloromethane/methanol/aqueous ammonia (20% by mass), 80/20/2, v/v/v). 0.049 g (yield=22%) of 2-(((3-((3-(trifluoromethyl)phenyl)ethynyl) imidazo[1,2-a]pyridin-2-yl)methyl)amino) acetic acid were obtained as a white solid. LC-MS: m/z=374 (MH+); UV purity at 254 nm=98%. 1H NMR (300 MHz, DMSO) δ 8.76 (d, J=6.7 Hz, 1H), 8.13 (s, 1H), 8.01 (d, J=7.6 Hz, 1H), 7.78 (d, J=7.9 Hz, 1H), 7.69 (dd, J=8.3, 7.1 Hz, 2H), 7.53-7.42 (m, 1H), 7.16 (td, J=6.8, 1.0 Hz, 1H), 4.17 (s, 2H), 3.31 (s, 6H).

Workup

  1. customIn a reactor equipped with
  2. filtrationa filter
  3. customdichloromethane was removed by filtration
  4. additionwas added
  5. stirringThe mixture was stirred under a slow vortex at r.t. for 24 h
  6. customThe resin was removed by filtration
  7. washwashed with 15 ml of methanol, 15 ml of dichloromethane
  8. concentrationThe obtained filtrate was concentrated in vacuo
  9. customthe residue was purified by flash chromatography on a silica gel cartridge (eluent: dichloromethane/methanol/aqueous ammonia (20% by mass), 80/20/2, v/v/v)

Sources & evidence

ORD record
ord-a51057c6292840d7bbd044bd9b500d4b
Source dataset
uspto-grants-2016_07
Patent number
US09381191B2

Reaction notes

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