Methyl chloroformate → HCID 71584705, compound

HRID 1430530Notes

Reaction equation

HRID 1430530 reaction equation
CS(O)(=O)=O.[NH2:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:20]3[C:21]([Cl:37])=[CH:22][C:23]([F:36])=[C:24]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:28])[CH:25]=3)[C:13](=[O:19])[N:14]2[CH2:17][CH3:18])=[CH:9][N:8]=1.[CH3:38][O:39][C:40](Cl)=[O:41]>N1C=CC=CC=1>[Cl:37][C:21]1[CH:22]=[C:23]([F:36])[C:24]([NH:26][C:27]([NH:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:28])=[CH:25][C:20]=1[C:12]1[C:13](=[O:19])[N:14]([CH2:17][CH3:18])[C:15]2[C:10]([CH:11]=1)=[CH:9][N:8]=[C:7]([NH:6][C:40](=[O:41])[O:39][CH3:38])[CH:16]=2

Participants

4

Reactant 2

HCID 6586Methyl chloroformate3×HCID 86713641HCID 86713641, compound

Product 1

HCID 71584705HCID 71584705, compoundYield 89.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of Example 21 (100 mg, 0.221 mmol) in pyridine (3 mL) was treated drop-wise with methylchloroformate (23 mg, 0.243 mmol) and stirred at RT for 4 h. Additional methylchloroformate (50 mL) was added and the mixture stirred overnight. The mixture was treated with additional methylchloroformate (100 mL) and stirred for another 2 days. The mixture was concentrated to dryness, treated with EtOAc and water and the resulting solid collected via filtration. The material was purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA); the organics were removed under reduced pressure and the aqueous mixture was neutralized with satd. NaHCO3. The resulting solid was collected via filtration, washed with water and dried to afford methyl (3-(2-chloro-4-fluoro-5-(3-phenylureido)phenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)carbamate (101 mg, 87% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.56 (br s, 1H), 9.31-8.78 (m, 2H), 8.67 (s, 1H), 8.20 (d, J=8.6 Hz, 1H), 7.96 (s, 2H), 7.56 (d, J=11.0 Hz, 1H), 7.42 (d, J=8.0 Hz, 2H), 7.26 (t, J=7.8 Hz, 2H), 6.96 (t, J=7.4 Hz, 1H), 4.20 (q, J=7.2 Hz, 2H), 3.71 (s, 3H), 1.25 (t, J=7.1 Hz, 3H); MS (ESI) m/z: 510.1 [M+H]+.

Workup

  1. stirringthe mixture stirred overnight
  2. stirringstirred for another 2 days
  3. concentrationThe mixture was concentrated to dryness
  4. additiontreated with EtOAc and water
  5. filtrationthe resulting solid collected via filtration
  6. customThe material was purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  7. customthe organics were removed under reduced pressure
  8. filtrationThe resulting solid was collected via filtration
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-e6247e03c1ce4938a0790480fa8e1705
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

Loading…