Trifluoroacetic acid → (R)-4-((R)-1-((1-cyclopropyl-5-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)-1H-benzo[d]imidazol-7yl)oxy)ethyl)pyrrolidin-2-one

HRID 2209123Notes

Reaction equation

HRID 2209123 reaction equation
[CH:1]1([N:4]2[C:8]3[C:9]([O:31][C@@H:32]([C@@H:34]4[CH2:38][C:37](=[O:39])[NH:36][CH2:35]4)[CH3:33])=[CH:10][C:11]([C:13]4[CH:22]=[C:21]5[C:16]([N:17]([CH3:30])[CH2:18][CH2:19][N:20]5C(OC(C)(C)C)=O)=[CH:15][CH:14]=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1([N:4]2[C:8]3[C:9]([O:31][C@@H:32]([C@H:34]4[CH2:35][NH:36][C:37](=[O:39])[CH2:38]4)[CH3:33])=[CH:10][C:11]([C:13]4[CH:22]=[C:21]5[C:16](=[CH:15][CH:14]=4)[N:17]([CH3:30])[CH2:18][CH2:19][NH:20]5)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117843390tert-butyl 7-(1-cyclopropyl-7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-1H-benzo[d]imidazol-5-yl)-4-methyl-3,4 dihydroquinoxaline-1(2H)-carboxylate

Product 1

HCID 117842886(R)-4-((R)-1-((1-cyclopropyl-5-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)-1H-benzo[d]imidazol-7yl)oxy)ethyl)pyrrolidin-2-oneYield 73.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-butyl 7-(1-cyclopropyl-7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-1H-benzo[d]imidazol-5-yl)-4-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (40 mg, 0.075 mmol) was dissolved in DCM (2 mL), TFA (0.29 mL, 3.76 mmol) was added. The reaction was stirred at rt for 16 h. The mixture was quenched with saturated NaHCO3, extracted with EtOAc (3×30 ml). The combined organic layers were washed with water (2×5 mL), concentrated and purified by flash chromatography eluted with 5% to 20% MeOH/EtOAc to give 23.8 mg, (73.3%) of (R)-4-((R)-1-((1-cyclopropyl-5-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)-1H-benzo[d]imidazol-7yl)oxy)ethyl)pyrrolidin-2-one:. 1H NMR (300 MHz, DMSO-d6) δ 8.01 (s, 1H), 7.57 (s, 1H), 7.19 (s, 1H), 6.88 (s, 1H), 6.74 (dd, J=2.4, 2.4 Hz, 1H), 6.68 (d, J=2.4 Hz, 1H), 6.48 (d, J=8.1 Hz, 1H), 5.54 (s, 1H), 4.76-4.73 (m, 1H), 3.67-3.63 (m, 1H), 3.40-3.30 (m, 3H), 3.20-3.11 (m, 3H), 2.77 (s, 4H), 2.38-2.23 (m, 2H), 1.29 (d, J=6 Hz, 3H), 1.06-0.96 (m, 4H), LCMS-ESI+ (m/z): [M+H]+ calcd for C25H29N5O2:431.23; found 432.22.

Workup

  1. customThe mixture was quenched with saturated NaHCO3
  2. extractionextracted with EtOAc (3×30 ml)
  3. washThe combined organic layers were washed with water (2×5 mL)
  4. concentrationconcentrated
  5. custompurified by flash chromatography
  6. washeluted with 5% to 20% MeOH/EtOAc

Sources & evidence

ORD record
ord-ef749f1097844bdcaa591ff568787b93
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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