Tetrafluoroborate → (S)-tert-butyl 2-(2-isopropoxy-9H-pyrimido[4,5-b]indol-6-yl)morpholine-4-carboxylate

HRID 710274Notes

Reaction equation

HRID 710274 reaction equation
Cl[C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C@@H:19]3[O:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]3)=[CH:15][CH:14]=2)=[N:4][C:5]([O:8][CH:9]([CH3:11])[CH3:10])=[N:6][CH:7]=1.F[B-](F)(F)F.C1CCN2C(=NCCC2)CC1>CC1C=CC=CC=1C.CN(C)C(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:9]([O:8][C:5]1[N:6]=[CH:7][C:2]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C@@H:19]4[O:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]4)[CH:17]=3)[NH:12][C:3]=2[N:4]=1)([CH3:11])[CH3:10]

Participants

7

Reactant 3

HCID 26255TetrafluoroborateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 89689489(S)-tert-butyl 2-(4-(5-chloro-2-isopropoxypyrimidin-4-ylamino)phenyl)morpholine-4-carboxylate

Product 1

HCID 89689464(S)-tert-butyl 2-(2-isopropoxy-9H-pyrimido[4,5-b]indol-6-yl)morpholine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 7237O-XyleneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
155 °C

Procedure

(S)-tert-Butyl 2-(4-(5-chloro-2-isopropoxypyrimidin-4-ylamino)phenyl)morpholine-4-carboxylate (55 mg, 0.12 mmol), palladium-(II) acetate (2.8 mg, 0.012 mmol), tricyclohexylphopsphine tetrafluoroborate (9 mg, 0.024 mmol) and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene; 37 mg, 0.245 mmol) were dissolved in a mixture of o-xylene (0.5 ml) and N,N-dimethylacetamide (0.5 ml). The mixture was degassed with Ar for 5 min, the vessel closed and heated at 155° C. for 16 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over MgSO4 and evaporated. The residue was purified by column chromatography (SiO2, 5 to 20% EtOAc in heptane, 2 g ISCO column). White solid (11 mg, 22%). MS (ISP): 413.3 ([M+H]+).

Workup

  1. customThe mixture was degassed with Ar for 5 min
  2. customthe vessel closed
  3. additionThe reaction mixture was poured into water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over MgSO4
  6. customevaporated
  7. customThe residue was purified by column chromatography (SiO2, 5 to 20% EtOAc in heptane, 2 g ISCO column)

Sources & evidence

ORD record
ord-52252135c09b4fd7aa2d2c73540156ef
Source dataset
uspto-grants-2015_11
Patent number
US09181230B2

Reaction notes

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