Potassium Phosphate, Tribasic → HCID 44611120, compound

HRID 1916086Notes

Reaction equation

HRID 1916086 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.C(N(CC)C(=O)C1C=CC=CC=1O)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:53][NH:54][CH2:55][CH2:56][N:57]([CH3:59])[CH3:58]>CN(C=O)C.C(OCC)(=O)C.O.[OH-].[NH4+].[Cu]I>[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:54]([CH2:55][CH2:56][N:57]([CH3:59])[CH3:58])[CH3:53])=[CH:3][CH:4]=4)[CH3:9])=[N:30][C:15]2=3)[CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

10

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 673381,2-Ethanediamine, N1,N1,N2-trimethyl-2×HCID 88006Diethylsalicylamide2×HCID 44612767HCID 44612767, compound

Product 1

HCID 44611120HCID 44611120, compoundYield 17.9%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
90 °C

Procedure

Into an oven dried Schlenk tube dried under Argon was added (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, 0.2096 mmol), CuI (1.996 mg, 0.01048 mmol), N,N-diethyl-2-hydroxy-benzamide (8.101 mg, 0.04192 mmol) and K3PO4 (88.98 mg, 0.4192 mmol). The tube was evacuated and re-filled with Argon (three times), and N,N′,N′-trimethylethane-1,2-diamine (32.12 mg, 40.87 μL, 0.3144 mmol) in DMF (1 mL) was added and the reaction mixture was heated to 90° C. for 96 h. Additional CuI (1.996 mg, 0.01048 mmol), N,N-diethyl-2-hydroxy-benzamide (8.101 mg, 0.04192 mmol) and N,N′,N′-trimethylethane-1,2-diamine (214.2 mg, 272.5 μL, 2.096 mmol) were added to the tube and the tube was re-charged with argon and heated to 90° C. overnight. The reaction mixture was then cooled to the ambient temperature and diluted with ethyl acetate (5 mL), water (5 mL) and ammonium hydroxide (0.2 mL). The aqueous layer was extracted with ethyl acetate (four times, 5 mL each), dried with MgSO4, filtered and concentrated in vacuo. The crude product was purified by mass directed HPLC and product fractions combined and passed through a bicarbonate cartridge and lyophilized to give the title compound as a white solid (18.5 mg, 17% yield).

Workup

  1. customInto an oven dried Schlenk tube
  2. customdried under Argon
  3. customThe tube was evacuated
  4. additionwas added
  5. additionthe tube was re-charged with argon
  6. temperatureheated to 90° C. overnight
  7. temperatureThe reaction mixture was then cooled to the ambient temperature
  8. extractionThe aqueous layer was extracted with ethyl acetate (four times, 5 mL each)
  9. dry with materialdried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified by mass

Sources & evidence

ORD record
ord-b94ee926c88248cc89e7b6357dc4f994
Source dataset
uspto-grants-2013_12
Patent number
US08618106B2

Reaction notes

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