Tri-o-tolylphosphine → (E)-3-(2-aminopyrimidin-5-yl)-N-methyl-N-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)acrylamide

HRID 18326Notes

Reaction equation

HRID 18326 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[CH3:9][N:10]([CH2:15][C:16]1[C:24]2[C:19](=[N:20][CH:21]=[CH:22][CH:23]=2)[N:18]([CH3:25])[CH:17]=1)[C:11](=[O:14])[CH:12]=[CH2:13].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(C(C)C)C(C)C>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[N:7]=[CH:6][C:5](/[CH:13]=[CH:12]/[C:11]([N:10]([CH3:9])[CH2:15][C:16]2[C:24]3[C:19](=[N:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH3:25])[CH:17]=2)=[O:14])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 2313102-Amino-5-bromopyrimidineHCID 22139100N-methyl-N-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)acrylamide

Product 1

HCID 9973420(E)-3-(2-aminopyrimidin-5-yl)-N-methyl-N-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)acrylamideYield 20%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

A solution of 2-amino-5-bromopyrimidine (0.27 g, 1.55 mmole), N-methyl-N-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)acrylamide (0.5 g, 2.33 mmole), Pd(OAc)2 (0.037 g, 0.163 mmole), P(o-tolyl)3 (0.085 g, 0.28 mmole), and (i-Pr)2NEt (0.42 mL, 2.33 mmole) in propionitrile (20 mL) was degassed then heated to reflux. After 18 hr the mixture was cooled to RT and concentrated. Flash chromatography on silica gel (10% MeOH/CH2Cl2) gave the title compound (0.100 g, 18%): MS (ES) m/e 363 (M+H)+.

Workup

  1. temperaturethen heated to reflux
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-03e5bbc4997841908c5f88cf5a5ca788
Source dataset
uspto-grants-2010_06
Patent number
US07741339B2

Reaction notes

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