HCID 89815853, compound → HCID 89815570, compound

HRID 1468896Notes

Reaction equation

HRID 1468896 reaction equation
[CH3:1][O:2][C:3](=[O:37])[C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[C:7]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=3)[C@H:15]([CH:29]([CH3:31])[CH3:30])[C:14]2=O)=[CH:6][C:5]=1[S:33]([CH3:36])(=[O:35])=[O:34]>C(O)(=O)C.[Fe]>[CH3:1][O:2][C:3]([C:4]1[C:5]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:6][C:7]2[N:13]3[CH2:18][CH2:17][N:16]([C:19]4[N:24]=[C:23]([C:25]([F:28])([F:26])[F:27])[CH:22]=[CH:21][N:20]=4)[CH:15]([CH:29]([CH3:31])[CH3:30])[C:14]3=[N:10][C:8]=2[CH:9]=1)=[O:37]

Participants

4

Reactant 1

HCID 89815853HCID 89815853, compound

Product 1

HCID 89815570HCID 89815570, compoundYield 51.4%

Reagents, catalysts & solvents 2

HCID 23925IronCatalyst2×HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-methyl-4-(3-isopropyl-2-oxo-4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)-2-(methylsulfonyl)-5-nitrobenzoate (1.45 g, 2.66 mmol) in glacial acetic acid (17 mL) was added iron powder (445 mg, 7.97 mmol). The mixture was heated to 100° C. After 5 min, the suspended iron dissolved into solution. The mixture was stirred at 100° C. for 48 h, at which point the flask was cooled to rt and the contents were poured into ice. The mixture was extracted with EtOAc (2×75 mL), then the combined organic layers were washed with water (2×50 mL) and brine (50 mL). The solution was dried over MgSO4, filtered through cotton, and concentrated in vacuo. The residue was purified on a silica cartridge (0% EtOAc in hexanes, then 50%) to yield 680 mg of methyl-1-isopropyl-7-(methylsulfonyl)-2-(4-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate as a racemic mixture (51%). LC-MS: m/z 498.32 (M+H]+. 1H NMR (CDCl3, 400 MHz): δ 8.58 (d, J=4.8 Hz, 1H), 8.20 (s, 1H), 8.12 (s, 1H), 6.90 (d, J=4.8 Hz, 1H), 6.13 (d, J=8.4 Hz, 1H), 5.39 (dd, J=4.8 Hz, 14.4 Hz, 1H), 4.35 (ddd, J=1.2 Hz, 4.4 Hz, 12.0 Hz, 1H), 4.21 (dt, J=4.8 Hz, 12.0 Hz, 1H), 4.00 (s, 3H), 3.78 (ddd, J=4.4 Hz, 11.6 Hz, 14.4 Hz, 1H), 3.45 (s, 3H), 2.48 (sept, J=7.2 Hz, 1H), 1.32 (d, J=6.4 Hz, 3H), 1.08 (d, J=6.8 Hz, 3H).

Workup

  1. temperaturewas cooled to rt
  2. additionthe contents were poured into ice
  3. extractionThe mixture was extracted with EtOAc (2×75 mL)
  4. washthe combined organic layers were washed with water (2×50 mL) and brine (50 mL)
  5. dry with materialThe solution was dried over MgSO4
  6. filtrationfiltered through cotton
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on a silica cartridge (0% EtOAc in hexanes

Sources & evidence

ORD record
ord-4014d8c939284765a37261e92fe4f755
Source dataset
uspto-grants-2015_04
Patent number
US09006244B2

Reaction notes

Loading…