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

HRID 1362135Notes

Reaction equation

HRID 1362135 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-4ea1c6d7f5fd431ab167cc1ea60e599d
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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