4-Methylmorpholine → N-[(2R)-1-Hydroxyhexan-2-yl]-2,6-dimethyl-8-(3-methylbutoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1844219Notes

Reaction equation

HRID 1844219 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([O:10][CH2:11][CH2:12][CH:13]([CH3:15])[CH3:14])=[CH:8][C:7]([CH3:16])=[CH:6][N:5]2[C:17]=1[C:18]([OH:20])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[NH2:50][C@H:51]([CH2:54][CH2:55][CH2:56][CH3:57])[CH2:52][OH:53]>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[OH:53][CH2:52][C@H:51]([NH:50][C:18]([C:17]1[N:5]2[CH:6]=[C:7]([CH3:16])[CH:8]=[C:9]([O:10][CH2:11][CH2:12][CH:13]([CH3:14])[CH3:15])[C:4]2=[N:3][C:2]=1[CH3:1])=[O:20])[CH2:54][CH2:55][CH2:56][CH3:57]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6994402(R)-2-Aminohexan-1-olHCID 86717930HCID 86717930, compound

Product 1

HCID 74222630N-[(2R)-1-Hydroxyhexan-2-yl]-2,6-dimethyl-8-(3-methylbutoxy)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22392675Trifluoroacetic acid waterSolvent

Procedure

75 mg (0.27 mmol) of 2,6-dimethyl-8-(3-methylbutoxy)imidazo[1,2-a]pyridine-3-carboxylic acid Example 89A, 96 mg (0.30 mmol) of TBTU and 110 mg (1.09 mmol) of 4-methylmorpholine were initially charged in 1.73 ml of DMF. 35 mg (0.30 mmol) of (R)-(−)-2-aminohexanol were then added, and the mixture was stirred at room temperature overnight. The reaction solution was diluted with water/TFA and purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The concentrated fractions were taken up in dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted two more times with dichloromethane, the combined organic phases were dried over sodium sulphate and filtered and the filtrate was concentrated and lyophilized. This gave 91 mg of the target compound (87.5% of theory, purity 98%).

Workup

  1. custompurified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
  2. washwashed twice with saturated aqueous sodium bicarbonate solution
  3. extractionThe aqueous phase was extracted two more times with dichloromethane
  4. dry with materialthe combined organic phases were dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-dee80a8240b44109b444387e3b5610ae
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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