4-Methylmorpholine → HCID 86718183, compound

HRID 1844158Notes

Reaction equation

HRID 1844158 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16](O)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.Cl.[NH2:25][C@H:26]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH2:28][CH2:29][CH3:30].F[B-](F)(F)F.CN([CH+]N(C)C)C.CN1CCOCC1>ClCCl>[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:25][C@H:26]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH2:28][CH2:29][CH3:30])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 14039065methyl (2S)-2-aminohexanoate hydrochlorideHCID 867178728-((2,6-Difluorobenzyl)oxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acidHCID 178484182HCID 178484182, compound

Product 1

HCID 86718183HCID 86718183, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

500 mg of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid (Example 6A; 1.57 mmol, 1 equivalent) were initially charged in 10 ml of anhydrous dichloromethane, and 313 mg of methyl L-norleucinate hydrochloride (1.73 mmol, 1.1 equivalents), 554 mg of benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU; 1.73 mmol, 1.1 equivalents) and 0.864 ml of 4-methylmorpholine (7.85 mmol, 5 equivalents) were added in succession. The reaction mixture was stirred at room temperature for 4 h. The mixture was then diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate solution, with water and finally with saturated aqueous sodium chloride solution, dried and concentrated. The residue obtained was chromatographed on a 100 g silica gel cartridge (Biotage Isolera; cyclohexane/ethyl acetate gradient as mobile phase). This gave 644 mg of the target compound (91% of theory).

Workup

  1. washwashed with saturated aqueous sodium bicarbonate solution, with water and finally with saturated aqueous sodium chloride solution
  2. customdried
  3. concentrationconcentrated
  4. customThe residue obtained
  5. customwas chromatographed on a 100 g silica gel cartridge (Biotage Isolera; cyclohexane/ethyl acetate gradient as mobile phase)

Sources & evidence

ORD record
ord-9e3121a782b745869db266daf675efcd
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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