HCID 89783988, compound → HCID 89782250, compound

HRID 1055982Notes

Reaction equation

HRID 1055982 reaction equation
COC1C=C(OC)C=CC=1C[N:6]1[CH2:11][CH2:10][N:9]2[CH:12]=[C:13]([C:15]3[CH:16]=[CH:17][CH:18]=[C:19]4[C:24]=3[N:23]=[C:22]([C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[O:26])[CH:21]=[CH:20]4)[CH:14]=[C:8]2[C:7]1=[O:33]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[N:27]1([C:25]([C:22]2[CH:21]=[CH:20][C:19]3[C:24](=[C:15]([C:13]4[CH:14]=[C:8]5[C:7](=[O:33])[NH:6][CH2:11][CH2:10][N:9]5[CH:12]=4)[CH:16]=[CH:17][CH:18]=3)[N:23]=2)=[O:26])[CH2:28][CH2:29][O:30][CH2:31][CH2:32]1

Participants

4

Reactant 1

HCID 89783988HCID 89783988, compound

Product 1

HCID 89782250HCID 89782250, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

The above-obtained brown solid 2-(2,4-dimethoxybenzyl)-7-(2-(morpholine-4-carbonyl)quinolin-8-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Example 167c) in 1 mL of TFA and 1 mL of DCM was heated in an oil bath at 50° C. for 1 h. The mixture was concentrated under reduced pressure. The orange residue was partitioned between 50 mL of EtOAc and 5 mL of 2 N NaOH. The EtOAc layer was washed with 10 mL of brine and concentrated. Purification of the brown residue on a silica gel column (1-10% MeOH in EtOAc) gave 7-(2-(morpholine-4-carbonyl)quinolin-8-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (80 mg, 0.213 mmol, 31% yield for 3 steps) as a tan crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.51 (1H, d, J=8.6 Hz), 8.07 (1H, dd, J=7.3, 1.3 Hz), 7.94 (1H, d, J=1.6 Hz), 7.86 (1H, m), 7.75 (2H, d, J=8.4 Hz), 7.67 (1H, t, J=7.7 Hz), 7.36 (1H, d, J=1.8 Hz), 4.23 (2H, m), 3.75 (4H, m), 3.64 (4H, m), 3.57 (2H, m). m/z (ESI, +ve) 377.0 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customThe orange residue was partitioned between 50 mL of EtOAc and 5 mL of 2 N NaOH
  3. washThe EtOAc layer was washed with 10 mL of brine
  4. concentrationconcentrated
  5. customPurification of the brown residue on a silica gel column (1-10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-1835629987664ed5a806721768cfe75a
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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