Tri-o-tolylphosphine → HCID 66967104, compound

HRID 1711931Notes

Reaction equation

HRID 1711931 reaction equation
C(OC([N:8]1[CH2:13][C:12](=[O:14])[NH:11][C:10]2[CH:15]=[C:16](Br)[CH:17]=[N:18][C:9]1=2)=O)(C)(C)C.[CH3:20][N:21]([CH2:26][C:27]1[N:28]([CH3:36])[C:29]2[C:34]([CH:35]=1)=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:22](=[O:25])[CH:23]=[CH2:24].C(N(C(C)C)CC)(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:20][N:21]([CH2:26][C:27]1[N:28]([CH3:36])[C:29]2[C:34]([CH:35]=1)=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:22](=[O:25])/[CH:23]=[CH:24]/[C:16]1[CH:17]=[N:18][C:9]2[NH:8][CH2:13][C:12](=[O:14])[NH:11][C:10]=2[CH:15]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 20752825N-Methyl-N-[(1-methyl-2-indolyl)methyl]acrylamideHCID 66966959HCID 66966959, compound

Product 1

HCID 66967104HCID 66967104, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 7-bromo-2-oxo-2,3-dihydro-1H-pyrido[2,3-b]pyrazine-4-carboxylic acid tert-butyl ester (494 mg, 1.5 mmol) in propionitrile (12 mL) was treated with N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-acrylamide (685 mg, 3 mmol) and diisopropylethylamine (788 μL, 4.5 mmol) and purged with Argon for 10 min. Pd(OAc)2 (34 mg, 0.15 mmol) and P(o-Tol)3 (92 mg, 0.3 mmol) was added and the Argon purge was repeated. The mixture was heated to 100° C. and stirred for 6 hours under Argon. Upon cooling, solvent was removed and the residue was purified by Flash chromatography (silica, 1-3% MeOH in CH2Cl2) to afford the title compound (480 mg, 67%). 1H NMR (300 MHz, DMSO-d6) δ 10.81 and 10.73 (rotamers, 2s, br, 1H), 8.46 and 8.41 (rotamers, 2s, 1H), 7.58 (d, J=15.4 Hz, 1H), 7.51 (m, 3H), 7.23 (d, J=15.4 Hz, 1H), 7.11 (m, 1H), 7.03 (m, 1H), 6.45 and 6.20 (rotamers, 2s, 1H), 5.06 and 4.87 (rotamers, 2s, 2H), 4.32 and 4.28 (rotamers, 2s, 2H), 3.74 and 3.71 (rotamers, 2s, 3H), 3.16 and 3.05 (rotamers, 2s, 3H), 1.44 and 1.42 (rotamers, 2s, 9H). MS (ESI) in/e: 476.2 (M+H)+, 420.2 (M-tert-Bu)+.

Workup

  1. custompurged with Argon for 10 min
  2. customthe Argon purge
  3. temperatureUpon cooling
  4. customsolvent was removed
  5. customthe residue was purified by Flash chromatography (silica, 1-3% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-af0dd49424e94f9eb48913d58c5544a1
Source dataset
uspto-grants-2010_09
Patent number
US07790709B2

Reaction notes

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