Cesium carbonate → tert-butyl 4-(1-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)azetidin-3-yl)piperazine-1-carboxylate

HRID 68684Notes

Reaction equation

HRID 68684 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([S:17][CH3:18])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.[NH:19]1[CH2:22][CH:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)[CH2:20]1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:18][S:17][C:6]1[C:5]2[C:9](=[CH:10][C:2]([N:19]3[CH2:22][CH:21]([N:23]4[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]4)[CH2:20]3)=[CH:3][CH:4]=2)[N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 21183794tert-Butyl 4-(azetidin-3-yl)piperazine-1-carboxylateHCID 67448855HCID 67448855, compound

Product 1

HCID 67449337tert-butyl 4-(1-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)azetidin-3-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 6-bromo-3-(methylthio)-1-phenyl-1H-indazole (300 mg, 0.94 mmol, 1.00 equiv) in toluene (20 mL), tert-butyl 4-(azetidin-3-yl)piperazine-1-carboxylate (270 mg, 1.12 mmol, 1.20 equiv), Cs2CO3 (430 mg, 1.32 mmol, 1.40 equiv), Pd(OAc)2 (a catalytic amount), BINAP (a catalytic amount). The resulting solution was heated to reflux overnight in an oil bath. The solids were filtered out. The filtrate was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1) to yield tert-butyl 4-(1-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)azetidin-3-yl)piperazine-1-carboxylate as a yellow solid. MS: 480 (MH+).

Workup

  1. customInto a 50-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureThe resulting solution was heated
  4. temperatureto reflux overnight in an oil bath
  5. filtrationThe solids were filtered out
  6. concentrationThe filtrate was concentrated under vacuum

Sources & evidence

ORD record
ord-0beb763fc720402ba1190a2035352297
Source dataset
uspto-grants-2014_09
Patent number
US08822447B2

Reaction notes

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