Tri-o-tolylphosphine → HCID 10096283, compound

HRID 1362160Notes

Reaction equation

HRID 1362160 reaction equation
Br[C:2]1[CH:15]=[N:14][C:5]2[NH:6][C:7](=[O:13])[C:8]([CH3:12])([CH3:11])[NH:9][CH2:10][C:4]=2[CH:3]=1.[CH3:16][N:17]([CH2:22][C:23]1[S:27][C:26]2[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=2[C:24]=1[CH3:32])[C:18](=[O:21])[CH:19]=[CH2:20].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:11][C:8]1([CH3:12])[C:7](=[O:13])[NH:6][C:5]2[N:14]=[CH:15][C:2](/[CH:20]=[CH:19]/[C:18]([N:17]([CH3:16])[CH2:22][C:23]3[S:27][C:26]4[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=4[C:24]=3[CH3:32])=[O:21])=[CH:3][C:4]=2[CH2:10][NH:9]1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 17930139N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamideHCID 594569147-Bromo-3,3-dimethyl-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 10096283HCID 10096283, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A suspension of 7-bromo-3,3-dimethyl-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.17 g, 0.63 mmol) in propionitrile (4 mL) and DMF (1 mL) was de-oxygenated with Ar for 10 min. The mixture was treated with N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamide (0.20 g, 0.81 mmol) and (i-Pr)2EtN (0.24 mL, 1.3 mmol) and was de-oxygenated with Ar for 5 min. Pd(OAc)2 (14 mg, 0.062 mmol) and P(o-tol)3 (38 mg, 0.12 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 5 min. The mixture was heated to reflux for 4 h, then allowed to cool. The resulting precipitate was isolated by filtration, washed with EtOAc, dissolved in CH2Cl2, and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2) gave the title compound (0.15 g, 56%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 8.97 (s, 1H), 8.45 (s, 1H), 7.77-7.65 (m, 3H), 7.53 (s, 1H), 7.40-7.29 (m, 2H), 6.98-6.84 (m, 1H), 4.94-4.89 (m, 2H), 4.02 (s, 2H), 3.15-3.10 (m, 3H), 2.43 (s, 3H), 1.70 (s, 1H), 1.49 (s, 6H); MS (ESI) m/e 435 (M+H)+.

Workup

  1. waitwas de-oxygenated with Ar for 5 min
  2. customfor 5 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 4 h
  5. temperatureto cool
  6. customThe resulting precipitate was isolated by filtration
  7. washwashed with EtOAc
  8. dissolutiondissolved in CH2Cl2
  9. customthe solvent was removed in vacuo
  10. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2)

Sources & evidence

ORD record
ord-4e6fa197c3d543f2b3df09bfe57df8bc
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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