Dimethylcarbamoyl Chloride → HCID 59548436, compound

HRID 1812263Notes

Reaction equation

HRID 1812263 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([NH2:24])[N:18]=3)=[CH:15][C:14]([CH:25]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[CH3:26])=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9].C(N(CC)CC)C.[CH3:40][N:41]([CH3:45])[C:42](Cl)=[O:43]>ClCCl>[NH2:24][C:19]1[N:20]=[C:21]([CH3:23])[N:22]=[C:17]([C:16]2[CH:15]=[C:14]([CH:25]([N:27]3[CH2:28][CH2:29][N:30]([C:42]([N:41]([CH3:45])[CH3:40])=[O:43])[CH2:31][CH2:32]3)[CH3:26])[CH:13]=[N:12][C:11]=2[NH:10][C:4]2[CH:5]=[N:6][C:7]([O:8][CH3:9])=[C:2]([F:1])[CH:3]=2)[N:18]=1

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 66612187HCID 66612187, compound

Product 1

HCID 59548436HCID 59548436, compoundYield 42.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(1-(piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.141 g, 0.321 mmol) in dichloromethane (5 mL) was chilled to 0° C. in an ice bath, then triethylamine (0.224 mL, 1.604 mmol) was added to the mixture while stirring. After 10 min, dimethylcarbamic chloride (Aldrich; 0.104 g, 0.962 mmol) was added into the mixture slowly via syringe. After the addition, the ice bath was removed and the mixture was allowed to stir under inert atmosphere overnight. The mixture was diluted with chloroform (20 mL) and water (10 mL). The organic layer was extracted with chloroform (3×10 mL). The combined organic extracts were dried (magnesium sulfate), filtered and concentrated in vacuo. The crude material was adsorbed onto silica gel and purified by chromatography through a silica-gel column (25 g) eluting with a 20% mixture of 10:1 methanol/ammonium hydroxide in dichloromethane to give 4-(1-(5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethyl)-N,N-dimethylpiperazine-1-carboxamide (0.070 g, 0.137 mmol, 42.7% yield) as a tan solid. 1H NMR (400 MHz, CDCl3) δ 12.34 (s, 1H) 9.40 (d, J=2.15 Hz, 1H) 8.17-8.23 (dd, 1H) 8.12 (d, J=2.54 Hz, 1H) 8.09 (d, J=2.15 Hz, 1H) 4.04 (s, 3H) 3.10-3.98 (m, 9H) 2.85 (s, 6H) 2.56 (s, 3H) 1.88 (d, J=6.85 Hz, 3H). m/z (ESI, +ve ion) 533 (M+Na)+.

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. stirringto stir under inert atmosphere overnight
  4. additionThe mixture was diluted with chloroform (20 mL) and water (10 mL)
  5. extractionThe organic layer was extracted with chloroform (3×10 mL)
  6. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by chromatography through a silica-gel column (25 g)
  10. washeluting with a 20% mixture of 10:1 methanol/ammonium hydroxide in dichloromethane

Sources & evidence

ORD record
ord-2f96303b62914cdcb4fd57d9e5ef636e
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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