Dichloromethane → HCID 71009006, compound

HRID 1626120Notes

Reaction equation

HRID 1626120 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[O:26][CH2:27][C:28]([F:49])([F:48])[C@:29]([C:32]3[CH:37]=[C:36](B4OCC(C)(C)CO4)[C:35]([F:46])=[CH:34][C:33]=3[F:47])([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.Cl[C:51]1[O:52][C:53]2[CH:59]=[C:58]([Cl:60])[CH:57]=[CH:56][C:54]=2[N:55]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>O1CCCC1.O>[CH3:23][O:22][C:19]1[CH:20]=[CH:21][C:16]([C:9]([NH:24][C:25]2[O:26][CH2:27][C:28]([F:48])([F:49])[C@:29]([C:32]3[CH:37]=[C:36]([C:51]4[O:52][C:53]5[CH:59]=[C:58]([Cl:60])[CH:57]=[CH:56][C:54]=5[N:55]=4)[C:35]([F:46])=[CH:34][C:33]=3[F:47])([CH3:31])[N:30]=2)([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 771752,6-DichlorobenzoxazoleHCID 71008756HCID 71008756, compound

Product 1

HCID 71009006HCID 71009006, compoundYield 50.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

In a tube a mixture of [bis-(4-methoxy-phenyl)-phenyl-methyl]-{(R)-4-[5-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-2,4-difluoro-phenyl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl}-amine (intermediate D1.1) (130 mg, 144 μmol), 2,6-dichlorobenzo[d]oxazole (30.4 mg, 159 μmol), and cesium carbonate (188 mg, 576 μmol) in tetrahydrofuran (4 ml) and water (2 ml) was purged with argon for 5 minutes. Thereafter, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (5.88 mg, 7.21 μmol) was added, the tube was sealed and the mixture heated at 80° C. for 16 hours. After evaporation, the residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 70:30 as the eluent. The [bis-(4-methoxy-phenyl)-phenyl-methyl]-{(R)-4-[5-(6-chloro-benzooxazol-2-yl)-2,4-difluoro-phenyl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl}-amine (52 mg, 50% yield) was obtained as a pale yellow solid. MS (ISP): m/z=716.1 [M+H]+.

Workup

  1. customwas purged with argon for 5 minutes
  2. customthe tube was sealed
  3. customAfter evaporation
  4. customthe residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 70:30 as the eluent

Sources & evidence

ORD record
ord-1674e76d42e9440fb305855f668e660c
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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