Methanol → HCID 89545461, compound

HRID 512116Notes

Reaction equation

HRID 512116 reaction equation
C[Si](C)(C)[O:3][C:4]1[N:13]=[C:12]([O:14][Si](C)(C)C)[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=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[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=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 12514465HCID 12514465, compoundHCID 22645461Methyl 5-(bromomethyl)-2-fluorobenzoate

Product 1

HCID 89545461HCID 89545461, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Similarly, compounds of this invention can be prepared as illustrated by the exemplary reaction in Scheme 2. Reaction of the intermediate 2,4-di(trimethylsiloxy)-5,6,7,8-tetrahydroquinazoline with methyl 5-(bromomethyl)-2-fluorobenzoate in DMF, followed by treatment with 1,4-dioxane and methanol, produced 1-(4-fluoro-3-methoxycarbonylbenzyl)-5,6,7,8-tetrahydroquinazol ine-2,4(1H,3H)-dione. Treatment of the ester with NaOH in water-methanol produced 1-(4-fluoro-3-carboxybenzyl)-5,6,7,8-tetrahydroquinazoline-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-(4-fluoro-3-(4-(cyclopentylcarbonyl)piperazine-1-carbonyl)benzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione.

Workup

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

Sources & evidence

ORD record
ord-160c86556e424751b835a631beb8141b
Source dataset
uspto-grants-2015_08
Patent number
US09102631B2

Reaction notes

Loading…