Indoline → 3-(2,3-Dihydro-indol-1-yl)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1505940Notes

Reaction equation

HRID 1505940 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Br[C:11]1[CH:33]=[N:32][C:14]2[N:15]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]3[CH:21]=[N:20][C:19]([C:22]#[N:23])=[CH:18][C:17]=3[C:13]=2[CH:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>C1(C)C=CC=CC=1>[N:1]1([C:11]2[CH:33]=[N:32][C:14]3[N:15]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:31])[CH3:30])[C:16]4[CH:21]=[N:20][C:19]([C:22]#[N:23])=[CH:18][C:17]=4[C:13]=3[CH:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 10328IndolineHCID 62657Potassium Phosphate, TribasicHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 58266568HCID 58266568, compound

Product 1

HCID 582666873-(2,3-Dihydro-indol-1-yl)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 54%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Indoline (67 mg, 0.56 mmol) was added to a solution of 3-bromo-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (210 mg, 0.52 mmol), tribasic potassium phosphate (164 mg, 0.77 mmol) and dicyclohexyl-(2′,6′-diisopropoxy-biphenyl-2-yl)-phosphane (88 mg, 0.19 mmol) in anhydrous toluene (5.0 mL). The reaction mixture was degassed with nitrogen for 10 minutes, heated at 110° C. for 18 h and then allowed to cool to ambient temperature. The resultant mixture was poured into water (40 mL) and extracted with DCM (2×40 mL). The combined organic phase was separated, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The resultant residue was purified by flash chromatography (silica, 12 g column, ISCO, 0-40% ethyl acetate in cyclohexane) and the isolated solid triturated with diethylether/pentane and air dried to afford the title compound as a yellow powder (124 mg, 54%). LCMS (Method B): RT=4.83 min, M±H+=442.

Workup

  1. customThe reaction mixture was degassed with nitrogen for 10 minutes
  2. temperatureto cool to ambient temperature
  3. additionThe resultant mixture was poured into water (40 mL)
  4. extractionextracted with DCM (2×40 mL)
  5. customThe combined organic phase was separated
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe resultant residue was purified by flash chromatography (silica, 12 g column, ISCO, 0-40% ethyl acetate in cyclohexane)
  10. customthe isolated solid triturated with diethylether/pentane and air
  11. customdried

Sources & evidence

ORD record
ord-5f1fc215629e41af8aa57c6dd0461329
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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