Potassium Phosphate, Tribasic → methyl 7-(morpholinosulfonyl)-2-phenyl-5H-pyrido[3,2-b]indole-4-carboxylate

HRID 2410868Notes

Reaction equation

HRID 2410868 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:11]1[CH:12]=[C:13]([C:33]([O:35][CH3:36])=[O:34])[C:14]2[NH:15][C:16]3[CH:17]=[C:18]([S:24]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)(=[O:26])=[O:25])[CH:19]=[CH:20][C:21]=3[C:22]=2[N:23]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2]>[O:30]1[CH2:31][CH2:32][N:27]([S:24]([C:18]2[CH:19]=[CH:20][C:21]3[C:22]4[N:23]=[C:11]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[CH:12]=[C:13]([C:33]([O:35][CH3:36])=[O:34])[C:14]=4[NH:15][C:16]=3[CH:17]=2)(=[O:26])=[O:25])[CH2:28][CH2:29]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86663069methyl 2-bromo-7-(morpholinosulfonyl)-5H-pyrido[3,2-b]indole-4-carboxylate

Product 1

HCID 66604846methyl 7-(morpholinosulfonyl)-2-phenyl-5H-pyrido[3,2-b]indole-4-carboxylateYield 90%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A mixture of phenylboronic acid (41.9 mg, 0.343 mmol),methyl 2-bromo-7-(morpholinosulfonyl)-5H-pyrido[3,2-b]indole-4-carboxylate (120 mg, 0.264 mmol), potassium phosphate tribasic (146 mg, 0.687 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (22 mg, 0.053 mmol), and Pd(OAc)2 (5.9 mg, 0.026 mmol) in a microwave vial was flushed with nitrogen. THF (1.3 mL) was added, the vial was capped and the reaction was heated in a 70° C. for 18 hr. It was partitioned between EtOAc and water and the organic phase was separated and washed with brine. It was dried with sodium sulfate and the solvent were removed. The residue was dissolved in DCM and radial chromatography (step gradient elution with DCM containing 0 to 10% EtOAc) afforded methyl 7-(morpholinosulfonyl)-2-phenyl-5H-pyrido[3,2-b]indole-4-carboxylate (107 mg, 0.237 mmol, 90% yield) as a yellow solid. MS (ESI) m/z 450.0 (M−H). 1H NMR (500 MHz, DMSO-d6) d ppm 12.04 (1H, s), 8.58 (1H, d, J=8.24 Hz), 8.47 (1H, s), 8.26 (2H, d, J=7.32 Hz), 8.19 (1H, d, J=1.22 Hz), 7.67 (1H, dd, J=8.24, 1.53 Hz), 7.58 (2H, t, J=7.63 Hz), 7.46-7.52 (1H, m), 4.11 (3H, s), 3.62-3.72 (4H, m), 2.92-3.00 (4H, m).

Workup

  1. customwas flushed with nitrogen
  2. additionTHF (1.3 mL) was added
  3. customthe vial was capped
  4. customIt was partitioned between EtOAc and water
  5. customthe organic phase was separated
  6. washwashed with brine
  7. dry with materialIt was dried with sodium sulfate
  8. customthe solvent were removed
  9. dissolutionThe residue was dissolved in DCM
  10. washradial chromatography (step gradient elution with DCM containing 0 to 10% EtOAc)

Sources & evidence

ORD record
ord-bb895f399727479fae69e0514ec9c4cb
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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