Dimethylcarbamoyl Chloride → HCID 69482781, compound

HRID 2364443Notes

Reaction equation

HRID 2364443 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:39])=[C:14]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:15](=[O:33])[N:16]3[CH2:19][CH2:20][N:21]([CH3:32])[C:22]([O:24]CC3C=CC=CC=3)=O)=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[CH:40]([N:43](C(C)C)[CH2:44]C)(C)C.CN(C)C(Cl)=O>C(Cl)Cl.[Pd]>[CH3:40][N:43]([CH3:44])[C:22]([N:21]([CH3:32])[CH2:20][CH2:19][N:16]1[C:17]2[C:12](=[N:11][CH:10]=[C:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH:18]=2)[C:13]([OH:39])=[C:14]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:15]1=[O:33])=[O:24]

Participants

6

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 81531DiisopropylethylamineHCID 69482645HCID 69482645, compound

Product 1

HCID 69482781HCID 69482781, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-1-[2-(methyl {[(phenylmethyl)oxy]carbonyl}amino)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate (0.255 g, 0.48 mmol) in CH2Cl2 (20 mL) was combined with diisopropylethylamine (0.42 mL, 2.4 mmol), dimethylcarbamic chloride (0.22 mL, 2.4 mmol) and Pd/C (0.030 g, 10% w/w). The resulting suspension was flushed with nitrogen and evacuated several times the charged with hydrogen under a balloon and stirred at ambient temperature overnight. The reaction mixture was filtered, washed with CH2Cl2, and concentrated in vacuo. The residue was washed with EtOAc:Hexanes 1:1, filtered and the filtrate was concentrated in vacuo. The residue was triturated with water and the resulting suspension was filtered to afford the title compound as an off-white crystalline solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.25 (t, J=7.05 Hz, 3 H), 2.59 (s, 6 H), 2.80 (s, 3 H), 3.26-3.30 (m, 2 H), 4.17 (s, 2 H), 4.23 (q, J=7.16 Hz, 2 H), 4.32 (t, J=6.21 Hz, 2 H), 7.11-7.18 (m, 2 H), 7.38-7.43 (m, 2 H), 8.11 (s, 1 H), 8.50 (d, J=1.47 Hz, 1 H); ES+ MS: 471 (M+H+).

Workup

  1. customThe resulting suspension was flushed with nitrogen
  2. customevacuated several times the
  3. additioncharged with hydrogen under a balloon
  4. filtrationThe reaction mixture was filtered
  5. washwashed with CH2Cl2
  6. concentrationconcentrated in vacuo
  7. washThe residue was washed with EtOAc:Hexanes 1:1
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated in vacuo
  10. customThe residue was triturated with water
  11. filtrationthe resulting suspension was filtered

Sources & evidence

ORD record
ord-e113d13546fd4dc7b01d3ccaad992e82
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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