Hydrochloric Acid → HCID 118036228, compound

HRID 1778101Notes

Reaction equation

HRID 1778101 reaction equation
C([O:4][CH2:5][C:6]([N:8]([CH2:10][C:11]1[C:12]([CH:36](OC)[O:37]C)=[N:13][C:14]2[N:15]([C:21](=[O:35])[NH:22][C:23]3[CH:28]=[C:27]([O:29][CH:30]([CH3:32])[CH3:31])[C:26]([C:33]#[N:34])=[CH:25][N:24]=3)[CH2:16][CH2:17][CH2:18][C:19]=2[CH:20]=1)[CH3:9])=[O:7])(=O)C.Cl>C1COCC1.O>[C:33]([C:26]1[C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[CH:28][C:23]([NH:22][C:21]([N:15]2[C:14]3[C:19](=[CH:20][C:11]([CH2:10][N:8]([CH3:9])[C:6](=[O:7])[CH2:5][OH:4])=[C:12]([CH:36]=[O:37])[N:13]=3)[CH2:18][CH2:17][CH2:16]2)=[O:35])=[N:24][CH:25]=1)#[N:34]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 118036314HCID 118036314, compound2×

Product 1

HCID 118036228HCID 118036228, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(((8-((5-cyano-4-isopropoxypyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)(methyl)amino)-2-oxoethyl acetate (intermediate 195, 378 mg, 0.682 mmol) in THF (1.7 ml) and water (1.7 ml) was added 37% aqueous HCl (1.12 mL, 13.64 mmol) at room temperature. The reaction mixture was stirred for 9.5 h at room temperature, quenched by the addition of saturated aqueous NaHCO3 and extracted with DCM (3×). The combined organic layers were dried using Na2SO4, filtered and evaporated. The crude product was dissolved in DMF, filtered to remove insoluble impurities and purified by reversed phase preparative HPLC eluting with a gradient of MeCN and water (RP 5, H2O/MeCN 95:05 to 00:100 in 20 min). Fractions containing the product were collected, concentrated, diluted with water and basified with NaHCO3. The mixture was extracted with DCM (2×), dried using Na2SO4, filtered and concentrated. The resulting reddish solid was triturated in MeCN, filtered and dried to yield the title compound as a white solid.

Workup

  1. customquenched by the addition of saturated aqueous NaHCO3
  2. extractionextracted with DCM (3×)
  3. customThe combined organic layers were dried
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe crude product was dissolved in DMF
  7. filtrationfiltered
  8. customto remove insoluble impurities
  9. custompurified by reversed phase preparative HPLC
  10. washeluting with a gradient of MeCN and water (RP 5, H2O/MeCN 95:05 to 00:100 in 20 min)
  11. additionFractions containing the product
  12. customwere collected
  13. concentrationconcentrated
  14. additiondiluted with water and basified with NaHCO3
  15. extractionThe mixture was extracted with DCM (2×)
  16. customdried
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customThe resulting reddish solid was triturated in MeCN
  20. filtrationfiltered
  21. customdried

Sources & evidence

ORD record
ord-06041e98042e4d8e88e1631783b5a431
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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