Water → HCID 67108746, compound

HRID 1432962Notes

Reaction equation

HRID 1432962 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][NH:16][CH2:15][C:14]3=[O:19])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH3:20][O:21][C:22]1[N:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[CH2:30]OC(=O)C)=[CH:24][CH:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>CC#N.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([CH2:30]/[CH:29]=[CH:28]/[C:25]4[CH:26]=[N:27][C:22]([O:21][CH3:20])=[CH:23][CH:24]=4)[CH2:15][C:14]3=[O:19])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11776TriphenylphosphineHCID 179851741-(4-Aminoquinazoline-7-ylmethyl)piperazine-2-oneHCID 69025161HCID 69025161, compound

Product 1

HCID 67108746HCID 67108746, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

Nitrogen (g) is bubbled through a solution of 1-(4-amino-quinazolin-7-ylmethyl)-piperazin-2-one (100 mg, 0.39 mmol), EXAMPLE 72, in 2 mL of CH3CN. After 5 min, acetic acid 3-(6-methoxy-pyridin-3-yl)-(E)-allyl ester (75 mg, 0.36 mmol, prepared as described in EXAMPLE 19 in 2 mL of CH3CN, palladium(II) acetate (catalytic amount), triphenylphosphine (catalytic amount), 2 mL of H2O and 0.5 mL of triethylamine are added to the solution. The mixture is heated at 80° C. for 1 hours. At this time, the mixture is cooled, filtered and concentrated in vacuo. The crude material is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 60% CH3CN/H2O (0.1% TFA) and the appropriate product fractions are combined and lyopholized to give the title compound (44 mg, 0.07 mmol) as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ9.86 (s, 1H), 9.79 (s, 1H), 8.83 (s, 1H), 8.40 (d, 1H), 8.25 (s, 1H), 7.95 (d, 1H), 7.75 (s, 1H), 7.63 (d, 1H), 6.86 (d, 1H), 6.82 (d, 1H), 6.32 (dt, 1H), 4.78 (s, 2H), 3.98 (s, 2H), 3.93 (m, 2H), 3.85 (s, 3H), 3.53 (m, 4H). ESI MS, [M+H]+=405.

Workup

  1. temperatureAt this time, the mixture is cooled
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe crude material is purified by RP-HPLC
  5. washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 60% CH3CN/H2O (0.1% TFA)

Sources & evidence

ORD record
ord-2cea7e53d59a4932ae5364592917c682
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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