Hydrochloric Acid → HCID 86713699, compound

HRID 1257282Notes

Reaction equation

HRID 1257282 reaction equation
[F:1][C:2]1[C:7]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:10])=[CH:6][C:5]([C:18]2[C:19](=[O:39])[N:20]([CH:36]([CH3:38])[CH3:37])[C:21]3[C:26]([CH:27]=2)=[CH:25][N:24]=[C:23]([NH:28][C:29](=[O:35])[O:30][C:31](C)([CH3:33])[CH3:32])[CH:22]=3)=[C:4]([CH3:40])[CH:3]=1.Cl.O1CCOCC1.ClC(OC(C)=C)=O>CO.O.N1C=CC=CC=1>[F:1][C:2]1[C:7]([NH:8][C:9]([NH:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:10])=[CH:6][C:5]([C:18]2[C:19](=[O:39])[N:20]([CH:36]([CH3:38])[CH3:37])[C:21]3[C:26]([CH:27]=2)=[CH:25][N:24]=[C:23]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])=[CH2:32])[CH:22]=3)=[C:4]([CH3:40])[CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 93846Isopropenyl chloroformateHCID 86713697HCID 86713697, compound

Product 1

HCID 86713699HCID 86713699, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

A solution of tert-butyl (3-(4-fluoro-2-methyl-5-(3-phenylureido)phenyl)-1-isopropyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)carbamate (0.2 g, 0.367 mmol) in MeOH (3 mL) was treated with HCl in dioxane (4 M, 0.916 mL, 3.67 mmol) and stirred at RT for 16 h. The mixture was concentrated to dryness, treated with pyridine (3 mL) and isopropenyl chloroformate (0.066 g, 0.550 mmol) and stirred at RT for 1 h. Water was added, the mixture stirred for several minutes, extracted with 20% THF/EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The residue was treated with 30% EtOAc/Hex, sonicated and the resulting solid collected via filtration to afford prop-1-en-2-yl (3-(4-fluoro-2-methyl-5-(3-phenylureido)phenyl)-1-isopropyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)carbamate (175 mg, 90% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.77 (s, 1H), 9.02 (s, 1H), 8.66 (s, 1H), 8.50 (s, 1H), 8.15 (s, 1H), 7.98 (d, J=8.5 Hz, 1H), 7.85 (s, 1H), 7.41 (d, J=8.0 Hz, 2H), 7.25 (t, J=7.8 Hz, 2H), 7.15 (d, J=12.2 Hz, 1H), 6.95 (t, J=7.3 Hz, 1H), 5.33 (m, 1H), 4.81 (s, 1H), 4.77 (s, 1H), 2.07 (s, 3H), 1.96 (s, 3H), 1.56 (d, J=7.0 Hz, 6H); MS (ESI) m/z: 530.2 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. stirringstirred at RT for 1 h
  3. stirringthe mixture stirred for several minutes
  4. extractionextracted with 20% THF/EtOAc (2×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. additionThe residue was treated with 30% EtOAc/Hex
  9. customsonicated
  10. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-8d666df99e474b45b2dda8580b927640
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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