Trifluoroacetic acid → HCID 178501127, compound

HRID 1486332Notes

Reaction equation

HRID 1486332 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[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([OH:17])=O)=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[NH2:54][CH2:55][C@H:56]1[CH2:61][CH2:60][C@H:59]([C:62]([O:64][CH3:65])=[O:63])[CH2:58][CH2:57]1.C(O)(C(F)(F)F)=O>CN(C=O)C.O>[F:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:2]([F:1])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([NH:54][CH2:55][C@H:56]3[CH2:57][CH2:58][C@H:59]([C:62]([O:64][CH3:65])=[O:63])[CH2:60][CH2:61]3)=[O:17])=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 117859510HCID 117859510, compoundHCID 178501118HCID 178501118, compound

Product 1

HCID 178501127HCID 178501127, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 100 mg (0.30 mmol, 1.0 eq.) of 7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 4A, 116 mg of TBTU (0.36 mmol, 1.2 eq.) and 0.132 ml (1.2 mmol, 4.0 eq.) of 4-methylmorpholine in 2.2 ml of DMF was admixed with 103 mg (0.60 mmol, 2.0 eq.) of methyl trans-4-(aminomethyl)cyclohexanecarboxylate, and the mixture was stirred at RT overnight. The reaction mixture was admixed with water and TFA and purified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA). The product fractions were combined and concentrated. Subsequently, the residue was taken up in dichloromethane and a little methanol, and washed twice with saturated aqueous sodium hydrogencarbonate solution. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered, concentrated and lyophilized. 67 mg of the target compound were obtained (46% of theory).

Workup

  1. custompurified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA)
  2. concentrationconcentrated
  3. washa little methanol, and washed twice with saturated aqueous sodium hydrogencarbonate solution
  4. extractionThe aqueous phase was extracted twice with dichloromethane
  5. dry with materialThe combined organic phases were dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-704db1d6c0654e1d9b42d877332def15
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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