Methanol → HCID 68388650, compound

HRID 927287Notes

Reaction equation

HRID 927287 reaction equation
C[Si](C)(C)[O:3][C:4]1[N:13]=[C:12]([O:14][Si](C)(C)C)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1.Br[CH2:22][C:23]1[CH:24]=[CH:25][C:26]([F:33])=[C:27]([CH:32]=1)[C:28]([O:30][CH3:31])=[O:29].O1CCOCC1.CO>CN(C=O)C>[F:33][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][N:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12](=[O:14])[NH:13][C:4]2=[O:3])=[CH:32][C:27]=1[C:28]([O:30][CH3:31])=[O:29]

Participants

6

Reactant 4

HCID 887MethanolHCID 312751,4-DioxaneHCID 11088105Quinazoline, 2,4-bis[(trimethylsilyl)oxy]-HCID 22645461Methyl 5-(bromomethyl)-2-fluorobenzoate

Product 1

HCID 68388650HCID 68388650, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compounds of this invention can be prepared as illustrated by the exemplary reaction in Scheme 2. Reaction of the intermediate 2,4-di(trimethylsiloxy)quinazoline with a substituted alkyl 3-(halomethyl)benzoate, such as methyl 5-(bromomethyl)-2-fluorobenzoate in DMF, followed by treatment with 1,4-dioxane and methanol, produced 1-(4-fluoro-3-methoxycarbonylbenzyl)quinazoline-2,4(1H,3H)-dione. Treatment of the ester with NaOH in water-methanol produced 1-(3-carboxy-4-fluorobenzyl)quinazoline-2,4(1H,3H)-dione. Coupling of the acid with a substituted amine, such as 1-cyclopentylcarbonylpiperazine, in the presence of coupling agents, such as HATU and DIPEA in DMF, produced the targeted compound 1-(3-(4-cyclopentylcarbonylpiperazine-1-carbonyl)-4-fluorobenzyl)quinazoline-2,4(1H,3H)-dione.

Workup

  1. customCompounds of this invention can be prepared
  2. customas illustrated by the exemplary reaction in Scheme 2

Sources & evidence

ORD record
ord-25a18ebc5a6841b2b737df13f3ef799c
Source dataset
uspto-grants-2016_03
Patent number
US09290460B2

Reaction notes

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