HCID 86704187, compound → HCID 86704200, compound

HRID 1497659Notes

Reaction equation

HRID 1497659 reaction equation
[C:1]([O:5][C:6](=[O:39])[NH:7][C:8]1[CH:13]=[C:12]([CH2:14][C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N:23]([S:27]([C:30]3[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=3[F:37])(=[O:29])=[O:28])[CH2:24][O:25][CH3:26])[C:18]=2[F:38])=O)[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].C1C=C[NH+]=CC=1.Br[Br-]Br.[CH:49]1([N:52]2[CH2:57][CH2:56][CH:55]([C:58](=[S:60])[NH2:59])[CH2:54][CH2:53]2)[CH2:51][CH2:50]1>CN(C=O)C>[CH:49]1([N:52]2[CH2:57][CH2:56][CH:55]([C:58]3[S:60][C:14]([C:12]4[CH:11]=[CH:10][N:9]=[C:8]([NH:7][C:6](=[O:39])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[CH:13]=4)=[C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]([S:27]([C:30]5[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=5[F:37])(=[O:29])=[O:28])[CH2:24][O:25][CH3:26])[C:18]=4[F:38])[N:59]=3)[CH2:54][CH2:53]2)[CH2:50][CH2:51]1

Participants

4

Reactant 2

HCID 86704187HCID 86704187, compoundHCID 131734220HCID 131734220, compound

Product 1

HCID 86704200HCID 86704200, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Tert-butyl-{4-[2-(3-{[(2,5-difluorophenyl)sulfonyl](methoxymethyl)amino}-2-fluorophenyl)-2-oxoethyl]pyridin-2-yl}carbamate (prepared as described in Example 9, 374 mg, 0.662 mmol) was dissolved in dry DMF (5 mL) under argon atmosphere. Pyridinium bromide perbromide (190 mg, 0.596 mmol, 0.9 eq) was added and the reaction mixture was stirred at r.t. for 50 min. 1-Cyclopropylpiperidine-4-carbothioamide (146 mg, 0.794 mmol, 1.2 eq) was then added and the mixture was heated to 70° C. After 1 h the reaction was allowed to cool to r.t. overnight. The solvent was concentrated under reduced pressure. The residue was taken up with ethyl acetate and washed with saturated aqueous NaHCO3 and brine. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatography on silica gel (DCM/MeOH 98:2) to give 290 mg (60%) of tert-butyl {4-[2-(1-cyclopropylpiperidin-4-yl)-4-(3-{[(2,5-difluorophenyl)sulfonyl](methoxymethyl)amino}-2-fluorophenyl)-1,3-thiazol-5-yl]pyridin-2-yl}carbamate as amorphous solid.

Workup

  1. temperaturethe mixture was heated to 70° C
  2. waitAfter 1 h the reaction was allowed
  3. temperatureto cool to r.t. overnight
  4. concentrationThe solvent was concentrated under reduced pressure
  5. washwashed with saturated aqueous NaHCO3 and brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customevaporated to dryness
  8. customThe crude product was purified by flash chromatography on silica gel (DCM/MeOH 98:2)

Sources & evidence

ORD record
ord-4f7cb17c60424884bf06a0e771e1637b
Source dataset
uspto-grants-2015_12
Patent number
US09199979B2

Reaction notes

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