1-Methylpiperazine → HCID 44611001, compound

HRID 2059594Notes

Reaction equation

HRID 2059594 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]2[N:12]=[CH:13][C:14]3[N:20]([CH3:21])[C:19](=[O:22])[C:18]([CH3:24])([CH3:23])[CH2:17][N:16]([CH:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)[C:15]=3[N:30]=2)[CH3:9])=[CH:4][CH:3]=1.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].COCCOC>[CH:25]1([N:16]2[CH2:17][C:18]([CH3:24])([CH3:23])[C:19](=[O:22])[N:20]([CH3:21])[C:14]3[CH:13]=[N:12][C:11]([NH:10][C@H:8]([C:5]4[CH:6]=[CH:7][C:2]([N:35]5[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]5)=[CH:3][CH:4]=4)[CH3:9])=[N:30][C:15]2=3)[CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 531671-MethylpiperazineHCID 62657Potassium Phosphate, TribasicHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 44612767HCID 44612767, compound

Product 1

HCID 44611001HCID 44611001, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

(S)-2-(1-(4-Bromophenyl)ethylamino)-9-cyclopentyl-5,7,7-trimethyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (100 mg, 0.2117 mmol), 1-methylpiperazine (84.82 mg, 93.93 μL, 0.8468 mmol), di-tert-butyl-(2-phenylphenyl)phosphane (6.317 mg, 0.02117 mmol) and K3PO4 (89.87 mg, 0.4234 mmol) were taken in up DME (2 mL) and degassed using cycles of vacuum and nitrogen. Pd2 DBA3 (19.39 mg, 0.02117 mmol) was added and the reaction mixture was further degassed and then heated at 100° C. in a sealed tube for 4 hours and then allowed to cool to the ambient temperature. The reaction mixture was then diluted with ethyl acetate (5 mL) and filtered. The filtrate was concentrated in vacuo and the residue purified by mass directed HPLC and the combined product fractions passed through a bicarbonate cartridge and lypholized to give the title compound as a white solid (9.9 mg, 10% yield).

Workup

  1. customdegassed
  2. customthe reaction mixture was further degassed
  3. temperatureto cool to the ambient temperature
  4. additionThe reaction mixture was then diluted with ethyl acetate (5 mL)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue purified by mass

Sources & evidence

ORD record
ord-b8d84403fa6745749c00a507d22537cd
Source dataset
uspto-grants-2012_10
Patent number
US08278297B2

Reaction notes

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