Dichloromethane → HCID 86641349, compound

HRID 1693316Notes

Reaction equation

HRID 1693316 reaction equation
S(Cl)(C)(=O)=[O:2].OC[CH2:8][C:9]1[C:18]2[CH2:17][S:16][N:15]=[C:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:13]3=[N:27][N:28]([CH2:30][C:31]4[C:36]([CH3:37])=[C:35]([O:38][CH3:39])[C:34]([CH3:40])=[CH:33][N:32]=4)[N:29]=[C:11]([C:12]=23)[CH:10]=1.ClCCl.[CH2:44]([N:46]([CH2:49][CH3:50])[CH2:47]C)[CH3:45]>>[CH3:39][O:38][C:35]1[C:34]([CH3:40])=[CH:33][N:32]=[C:31]([CH2:30][N:28]2[N:29]=[C:11]3[CH:10]=[C:9]([CH2:8][CH2:47][N:46]4[CH2:49][CH2:50][O:2][CH2:45][CH2:44]4)[C:18]4[CH2:17][S:16][N:15]=[C:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[C:13]([C:12]=43)=[N:27]2)[C:36]=1[CH3:37]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86641346HCID 86641346, compound

Product 1

HCID 86641349HCID 86641349, compoundYield 60%

Conditions

Temperature
0 °C

Procedure

Mesyl chloride (5 μl) was added dropwise to a mixture composed of tert-butyl {8-(2-hydroxyethyl)-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-2,7-dihydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-4-yl}carbamate of Example 134 (25 mg), dehydrated dichloromethane (0.5 ml) and triethylamine (15 μl) under ice-cooling, and the mixture was stirred at 0° C. for 10 minutes. After confirming that the raw material disappeared, the solvent in the reaction mixture was evaporated by spraying. Dioxane (0.2 ml) and morpholine (44 μl) as an amine were added to the residue, and the mixture was stirred at 60° C. for six hours. The reaction mixture was concentrated under reduced pressure, and a 0.5 N sodium hydroxide solution was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was concentrated, and the resulting residue was purified by NH silica gel column chromatography (hexane-ethyl acetate) to obtain the title compound (17 mg, 60%) as an oil.

Workup

  1. temperaturecooling
  2. customthe solvent in the reaction mixture was evaporated
  3. additionDioxane (0.2 ml) and morpholine (44 μl) as an amine were added to the residue
  4. stirringthe mixture was stirred at 60° C. for six hours
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additiona 0.5 N sodium hydroxide solution was added to the resulting residue
  7. extractionfollowed by extraction with ethyl acetate
  8. concentrationThe organic layer was concentrated
  9. customthe resulting residue was purified by NH silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-770450bbee11478d910123070e4f0e9d
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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