2-(tert-butylamino)-8-(2-(2,4-dimethoxybenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-3-methylquinazolin-4(3H)-one → 2-(tert-butylamino)-3-methyl-8-(1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-4(3H)-quinazolinone

HRID 1056325Notes

Reaction equation

HRID 1056325 reaction equation
[C:1]([NH:5][C:6]1[N:15]([CH3:16])[C:14](=[O:17])[C:13]2[C:8](=[C:9]([C:18]3[CH:19]=[C:20]4[C:25](=[O:26])[N:24](CC5C=CC(OC)=CC=5OC)[CH2:23][CH2:22][N:21]4[CH:38]=3)[CH:10]=[CH:11][CH:12]=2)[N:7]=1)([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[C:1]([NH:5][C:6]1[N:15]([CH3:16])[C:14](=[O:17])[C:13]2[C:8](=[C:9]([C:18]3[CH:19]=[C:20]4[C:25](=[O:26])[NH:24][CH2:23][CH2:22][N:21]4[CH:38]=3)[CH:10]=[CH:11][CH:12]=2)[N:7]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 897819382-(tert-butylamino)-8-(2-(2,4-dimethoxybenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-3-methylquinazolin-4(3H)-one

Product 1

HCID 897821402-(tert-butylamino)-3-methyl-8-(1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-4(3H)-quinazolinoneYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 2-(tert-butylamino)-8-(2-(2,4-dimethoxybenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-3-methylquinazolin-4(3H)-one (449a) (10 mg, 0.02 mmol) in 1 mL of DCM and 0.2 mL of TFA was heated in an oil bath at 50° C. for 4 h. The reaction mixture was concentrated under reduced pressure. The brown residue was partitioned between 25 mL of EtOAc and 3 mL of 0.5 N NaOH. The EtOAc layer was separated, washed with 5 mL of brine, and concentrated. The residue was purified on a silica gel column (1-5% MeOH in DCM) to afford 2-(tert-butylamino)-3-methyl-8-(1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)quinazolin-4(3H)-one (449) (5 mg, 70% yield) as an off white crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.77 (1H, dd, J=7.8, 1.6 Hz), 7.70 (1H, dd, J=7.4, 1.6 Hz), 7.64 (1H, d, J=1.6 Hz), 7.60 (1H, br.), 7.10 (1H, d, J=1.6 Hz), 7.06 (1H, t, J=7.6 Hz), 5.74 (1H, s), 4.06 (2H, m), 3.46 (2H, t, J=7.1 Hz), 3.39 (3H, s), 1.45 (9H, s). m/z (ESI, +ve) 366.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe brown residue was partitioned between 25 mL of EtOAc and 3 mL of 0.5 N NaOH
  3. customThe EtOAc layer was separated
  4. washwashed with 5 mL of brine
  5. concentrationconcentrated
  6. customThe residue was purified on a silica gel column (1-5% MeOH in DCM)

Sources & evidence

ORD record
ord-0211c36493e644699af654a5ad069ce9
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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