4-Methylmorpholine → HCID 86717977, compound

HRID 2275891Notes

Reaction equation

HRID 2275891 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:13]([C:17]([OH:19])=O)=[C:14]([CH3:16])[N:15]=2)[CH:9]=[C:10]([F:12])[CH:11]=1.F[B-](F)(F)F.N1(O[C+](N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:54][CH2:55][C:56]([NH2:59])([CH3:58])[CH3:57]>CN(C=O)C.O>[NH2:59][C:56]([CH3:58])([CH3:57])[CH2:55][NH:54][C:17]([C:13]1[N:8]2[CH:9]=[C:10]([F:12])[CH:11]=[C:6]([O:5][CH2:4][C:3]3[C:2]([F:1])=[CH:23][CH:22]=[CH:21][C:20]=3[F:24])[C:7]2=[N:15][C:14]=1[CH3:16])=[O:19]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 131282-Methylpropylenediamine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 86717875HCID 86717875, compoundHCID 178484679HCID 178484679, compound

Product 1

HCID 86717977HCID 86717977, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

45 mg of 8-[(2,6-difluorobenzyl)oxy]-6-fluoro-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 11A, 0.13 mmol, 1 equivalent), 65 mg of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU, 0.2 mmol, 1.5 equivalents) and 54 mg of 4-methylmorpholine (0.54 mmol, 4 equivalents) were initially charged in 0.9 ml of DMF. After 10 min at RT, 24 mg of 1,2-diamino-2-methylpropane (0.27 mmol, 2 equivalents) were added and the mixture was stirred at RT overnight. Another 22 mg equivalents of TBTU (0.07 mmol, 0.5 equivalents) and 12 mg of 1,2-diamino-2-methylpropane (0.13 mmol, 1 equivalent) were added and the reaction was stirred at RT for 2 h. Water was added and the reaction solution was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The residue was taken up in dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted twice with dichloromethane and the combined organic phases were dried over sodium sulphate. The mixture was filtered and concentrated and the crude product obtained was purified by thick-layer chromatography (mobile phase: dichloromethane/2 N ammonia in methanol: 10:0.5). This gave 31 mg of the title compound (55% of theory; purity 98%).

Workup

  1. stirringthe reaction was stirred at RT for 2 h
  2. customthe reaction solution was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
  3. washwashed twice with saturated aqueous sodium bicarbonate solution
  4. extractionThe aqueous phase was extracted twice with dichloromethane
  5. dry with materialthe combined organic phases were dried over sodium sulphate
  6. filtrationThe mixture was filtered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1d749e3508a4448b9609af9a36b6cef4
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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