Ethyl bromopyruvate → HCID 89689564, compound

HRID 877541Notes

Reaction equation

HRID 877541 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17](=[S:19])[NH2:18])=[C:13]([NH:20][CH:21]([CH3:23])[CH3:22])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[CH3:24][CH2:25][O:26][C:27]([C:29]([CH2:31]Br)=O)=[O:28]>CN(C=O)C>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[S:19][CH:31]=[C:29]([C:27]([O:26][CH2:25][CH3:24])=[O:28])[N:18]=4)=[C:13]([NH:20][CH:21]([CH3:23])[CH3:22])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

4

Reactant 2

HCID 66144Ethyl bromopyruvateHCID 89689796HCID 89689796, compound

Product 1

HCID 89689564HCID 89689564, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridine-3-carbothioamide (20) (30 mg, 0.08 mmol) and ethyl bromo pyruvate (0.17 mmol, 2 equiv.) were taken in DMF (5 mL) and heated at 100° C. for 3 h. The reaction mixture was then concentrated under reduced pressure to remove excess of DMF. The residue was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc twice. The organic layers were collected, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by column chromatography through silica gel and MeOH: CHCl3 as eluent to afford ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)thiazole-4-carboxylate. 1H NMR: 400 MHz, CD3OD: δ 1.34 (d, J=20.00 Hz, 6H), 1.43 (t, J=7.20 Hz, 3H), 3.75-3.77 (m, 1H), 4.41 (q, J=7.20 Hz, 2H), 6.16 (s, 1H), 7.54 (dd, J=2.00, 8.8 Hz, 1H), 7.97 (d, J=8.80 Hz, 1H), 8.21 (s, 1H), 8.43 (s, 1H), 9.07 (s, 1H). LC/MS: Ascentis Express C18, 5×2.1 mm-2.7 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 3 min; retention time: 2.131 min; LCMS (ES-API), m/z 440.0 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 7.409 min; Purity: 98%.

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. customto remove excess of DMF
  3. additionThe residue was diluted with EtOAc
  4. washwashed with water
  5. extractionThe aqueous layer was extracted with EtOAc twice
  6. customThe organic layers were collected
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material obtained
  11. customwas purified by column chromatography through silica gel and MeOH

Sources & evidence

ORD record
ord-07ee2e8c5de349cb84d6f6373139f4b0
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

Loading…