4-Methylmorpholine → HCID 90115443, compound

HRID 1624126Notes

Reaction equation

HRID 1624126 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.F[B-](F)(F)F.N1(O[C+](N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:53][CH:54]([C:57]1[CH:62]=[CH:61][C:60]([F:63])=[C:59]([F:64])[CH:58]=1)[CH2:55][OH:56]>ClCCl>[F:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:2]([F:1])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:53][CH:54]([C:57]3[CH:62]=[CH:61][C:60]([F:63])=[C:59]([F:64])[CH:58]=3)[CH2:55][OH:56])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 220488782-Amino-2-(3,4-difluorophenyl)ethanolHCID 867178728-((2,6-Difluorobenzyl)oxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acidHCID 178484679HCID 178484679, compound

Product 1

HCID 90115443HCID 90115443, compoundYield 3.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

100 mg (0.31 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 111 mg (0.35 mmol) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU) and 159 mg (1.57 mmol) of 4-methylmorpholine were initially charged in 2.0 ml of dichloromethane. After 10 min at RT, 142 mg (0.35 mmol) of 2-amino-2-(3,4-difluorophenyl)-ethanol were added and the mixture was stirred at room temperature overnight. The reaction solution was concentrated, and acetonitrile/methanol/water was added. A solid precipitated out, and this solid was filtered off and purified by chromatography on silica gel (mobile phase: dichloromethane:THF=10:1→5:1). The combined product fractions were concentrated and then triturated with acetonitrile, and the solid was filtered off and washed with methanol. This gave 39 mg of the target compound (26% of theory, purity 95%). After some time, the filtrate produced more solid; this gave another 5 mg of the target compound (3.3% of theory, purity 99%).

Workup

  1. concentrationThe reaction solution was concentrated
  2. additionacetonitrile/methanol/water was added
  3. customA solid precipitated out
  4. filtrationthis solid was filtered off
  5. custompurified by chromatography on silica gel (mobile phase: dichloromethane:THF=10:1→5:1)
  6. concentrationThe combined product fractions were concentrated
  7. customtriturated with acetonitrile
  8. filtrationthe solid was filtered off
  9. washwashed with methanol
  10. customAfter some time, the filtrate produced more solid

Sources & evidence

ORD record
ord-7d7cc4b414d942d6b6e5bb4bb67e5e4d
Source dataset
uspto-grants-2014_07
Patent number
US08778964B2

Reaction notes

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