Sodium Carbonate → 2-(1H-indol-5-yl)-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxamide

HRID 2410902Notes

Reaction equation

HRID 2410902 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:23]([NH2:25])=[O:24])[C:5]2[NH:6][C:7]3[CH:8]=[C:9]([C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[O:16])[CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]3[C:40](=[CH:41][CH:42]=2)[NH:39][CH:38]=[CH:37]3)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C([O-])([O-])=O.[Na+].[Na+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.C1(C)C=CC=CC=1.C1COCC1>[NH:39]1[C:40]2[C:36](=[CH:35][C:34]([C:2]3[CH:3]=[C:4]([C:23]([NH2:25])=[O:24])[C:5]4[NH:6][C:7]5[CH:8]=[C:9]([C:15]([N:17]6[CH2:18][CH2:19][O:20][CH2:21][CH2:22]6)=[O:16])[CH:10]=[CH:11][C:12]=5[C:13]=4[N:14]=3)=[CH:42][CH:41]=2)[CH:37]=[CH:38]1

Participants

11

Reactant 5

HCID 10340Sodium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 27347725-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 866630712-bromo-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxamide

Product 1

HCID 666046882-(1H-indol-5-yl)-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxamide

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

2-Bromo-7-(morpholine-4-carbonyl)-5H-pyrido[3,2-b]indole-4-carboxamide (60 mg, 0.149 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (72.3 mg, 0.298 mmol), Potassium phosphate tribasic (134 mg, 0.476 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (24.43 mg, 0.060 mmol) and Pd(OAc)2 (6.68 mg, 0.030 mmol) were mixed with THF (2 mL) in a sealed microwave vial. The mixture was flushed with N2 and heated at 85° C. in an oil bath for 3.5 hr. LC/MS showed there was trace amount of product formed. The reaction mixture was blown to dryness under N2 blower. To the mixture was added Pd(Ph3P)4 (34.4 mg, 0.030 mmol), Toluene (3 mL), MeOH (1.5 mL) and Na2CO3 (2M) (0.149 mL, 0.298 mmol). The mixture was then heated at 100° C. for 3 hrs. The mixture was concentrated and purified using preparative HPLC to give titled product. MS (ESI) m/z 440.3 (M+H)+. 1H NMR (DMSO-d6) δ ppm 11.65 (s, 1H), 11.20 (s, 1H), 8.67 (s, 1H), 8.5 (m, 2H), 8.32 (d, 1H, J=8.2), 8.12 (d, 1H, J=8.5), 7.9 (s, 1H), 7.8 (s, 1H), 7.53(d, 1H, J=8.0), 7.41(m, 1H), 7.30 (d, 1H, J=8.0), 6.57 (s, 1H), 3.66 (bs, 8H).

Workup

  1. customThe mixture was flushed with N2
  2. customformed
  3. temperatureThe mixture was then heated at 100° C. for 3 hrs
  4. concentrationThe mixture was concentrated
  5. custompurified

Sources & evidence

ORD record
ord-6557ff14ff61491aaf6560c99c62f6be
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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