Potassium Phosphate, Tribasic → HCID 66604320, compound

HRID 2410763Notes

Reaction equation

HRID 2410763 reaction equation
[CH3:1][O:2][C:3]1[CH:44]=[CH:43][C:6]([CH2:7][N:8]2[C:16]3[CH:15]=[C:14](OS(C(F)(F)F)(=O)=O)[CH:13]=[CH:12][C:11]=3[C:10]3[N:25]=[C:26]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=4)[CH:27]=[C:28]([C:29]([O:31][CH3:32])=[O:30])[C:9]2=3)=[CH:5][CH:4]=1.[CH3:45][C@H:46]1[O:51][C@@H:50]([CH3:52])[CH2:49][NH:48][CH2:47]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:45][C@H:46]1[CH2:47][N:48]([C:14]2[CH:13]=[CH:12][C:11]3[C:10]4[N:25]=[C:26]([C:33]5[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:40])[F:41])[CH:34]=5)[CH:27]=[C:28]([C:29]([O:31][CH3:32])=[O:30])[C:9]=4[N:8]([CH2:7][C:6]4[CH:43]=[CH:44][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[C:16]=3[CH:15]=2)[CH2:49][C@@H:50]([CH3:52])[O:51]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6415002,6-Dimethylmorpholine, cis-HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 86663028HCID 86663028, compound

Product 1

HCID 66604320HCID 66604320, compoundYield 56.3%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

A microwave vial containing a mixture of methyl 5-(4-methoxybenzyl)-2-(3-(trifluoromethyl)phenyl)-7-(trifluoromethylsulfonyloxy)-5H-pyrido[3,2-b]indole-4-carboxylate (51 mg, 0.08 mmol), cis-2,6-dimethylmorpholine (9.8 μL, 0.080 mmol), powdered potassium phosphate, tribasic (51 mg, 0.240 mmol), biphenyl-2-yldi-tert-butylphosphine (11 mg, 0.036 mmol), and Pd(OAc)2 (2.7 mg, 0.012 mmol) was flushed with nitrogen. DME (160 μL) was added and the vial was sealed and heated at 80° C. for 24 hr. The reaction was then partitioned between EtOAc and water and the organic phase was washed with brine and dried with sodium sulfate. The solvent was removed and the residue was chromatographed (step gradient elution with hexane containing 50 to 100% DCM) to afford methyl 7-((2S,6R)-2,6-dimethylmorpholino)-5-(4-methoxybenzyl)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (27 mg, 0.045 mmol, 56% yield) as a yellow oil. MS (ESI) m/z 604.40 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 8.40 (1H, s), 8.28-8.35 (2H, m), 7.88 (1H, s), 7.56-7.65 (2H, m), 7.03 (1H, dd, J=8.70, 1.98 Hz), 6.89 (2H, d, J=8.55 Hz), 6.81 (1H, d, J=1.83 Hz), 6.72-6.77 (2H, m), 5.66 (2H, s), 3.80-3.89 (2H, m), 3.80 (3H, s), 3.72 (3H, s), 3.54-3.62 (2H, m), 2.54 (2H, m), 1.28 (6H, d, J=6.1).

Workup

  1. additionA microwave vial containing
  2. customwas flushed with nitrogen
  3. additionDME (160 μL) was added
  4. customthe vial was sealed
  5. customThe reaction was then partitioned between EtOAc and water
  6. washthe organic phase was washed with brine
  7. dry with materialdried with sodium sulfate
  8. customThe solvent was removed
  9. customthe residue was chromatographed
  10. wash(step gradient elution with hexane containing 50 to 100% DCM)

Sources & evidence

ORD record
ord-fee1341d5e474d219e828e1ce8a912e2
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…