1,8-Diazabicyclo(5.4.0)undec-7-ene → methyl 2-((1R,3S)-3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)cyclohexylamino)oxazole-4-carboxylate

HRID 527083Notes

Reaction equation

HRID 527083 reaction equation
[F:1][C:2]1[C:3]([NH:28][C@H:29]2[CH2:34][CH2:33][CH2:32][C@@H:31]([NH2:35])[CH2:30]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10]([S:18]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:9]=2)=[N:6][CH:7]=1.FC1C=CC(C2C3C(=NC=C(F)C=3)NC=2)=CC=1N[C@H]1CCC[C@@H](N)C1.Cl[C:62]1[O:63][CH:64]=[C:65]([C:67]([O:69][CH3:70])=[O:68])[N:66]=1.C1CCN2C(=NCCC2)CC1>CN(C=O)C.CCOC(C)=O.O>[F:1][C:2]1[C:3]([NH:28][C@H:29]2[CH2:34][CH2:33][CH2:32][C@@H:31]([NH:35][C:62]3[O:63][CH:64]=[C:65]([C:67]([O:69][CH3:70])=[O:68])[N:66]=3)[CH2:30]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10]([S:18]([C:21]3[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=3)(=[O:19])=[O:20])[CH:9]=2)=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 16427154Methyl 2-chloro-1,3-oxazole-4-carboxylateHCID 68007103(1S,3R)-N1-[5-fluoro-2-[5-fluoro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-4-yl]cyclohexane-1,3-diamineHCID 68007687(1S,3R)-N1-(2-fluoro-5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)cyclohexane-1,3-diamine

Product 1

HCID 68007726methyl 2-((1R,3S)-3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)cyclohexylamino)oxazole-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1S,3R)—N1-[5-fluoro-2-[5-fluoro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-4-yl]cyclohexane-1,3-diamine, 44e, (0.089 g, 0.178 mmol) in DMF (1.5 mL) was added methyl 2-chlorooxazole-4-carboxylate (0.031 g, 0.195 mmol), followed by DBU (0.029 mL, 0.195 mmol). The reaction mixture was allowed to stir at room temperature overnight. The reaction was warmed to 75° C. and allowed to stir for 3 hours. Added an additional 16 mg of the chlorooxazole ester and the reaction was heated at 75° C. overnight. The mixture was diluted into water and EtOAc. The layers were separated and the organic phase was washed with brine, dried over MgSO4, filtered and evaporated to dryness. The crude residue was purified by silica gel chromatography (0-20% MeOH/CH2Cl2) to afford 28 mg of desired product: LCMS RT=3.73 (M+1) 624.12.

Workup

  1. temperatureThe reaction was warmed to 75° C.
  2. stirringto stir for 3 hours
  3. temperaturethe reaction was heated at 75° C. overnight
  4. customThe layers were separated
  5. washthe organic phase was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe crude residue was purified by silica gel chromatography (0-20% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-8e82da26276446c7a2a64858d1852395
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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