Methanol → HCID 25158768, compound

HRID 1714842Notes

Reaction equation

HRID 1714842 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]([CH2:14][C:15]2[C:20]([CH3:21])=[C:19]([O:22][CH3:23])[C:18]([CH3:24])=[CH:17][N:16]=2)[CH2:9][C:10]([O:12]C)=O)[C:5]([N+:25]([O-])=O)=[C:4]([S:28][CH3:29])[N:3]=1.CO>C(O)(=O)C.C(Cl)Cl.[Fe]>[NH2:1][C:2]1[N:3]=[C:4]([S:28][CH3:29])[C:5]2[NH:25][C:10](=[O:12])[CH2:9][N:8]([CH2:14][C:15]3[C:20]([CH3:21])=[C:19]([O:22][CH3:23])[C:18]([CH3:24])=[CH:17][N:16]=3)[C:6]=2[N:7]=1

Participants

6

Reactant 2

HCID 887MethanolHCID 59465208HCID 59465208, compound2×

Product 1

HCID 25158768HCID 25158768, compoundYield 28.7%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 2-[(2-amino-6-methylsulfanyl-5-nitro-pyrimidin-4-yl)-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methyl]amino]acetate (Intermediate 26)(212 mg) in glacial acetic acid (5 mL) stirred at 70° C. was added iron powder (120 mg). The reaction mixture was heated at 70° C. for 30 minutes then allowed to cool to room temperature. The reaction mixture was filtered, the filtrate evaporated to dryness and azeotroped with toluene to give a brown gum. This material was stirred with 5% methanol in DCM (10 mL) and then filtered to remove iron residues. The filtrate was purified by flash chromatography on silica eluting with an increasingly polar gradient of methanol/DCM (0/100 to 5/95) to give the title compound (52 mg) as a beige solid. 1H NMR spectrum (400 MHz, DMSO-d6) 2.11 (6H, s), 2.37 (3H, s), 3.66 (3H, s), 3.88 (2H, s), 4.68 (2H, s), 5.80 (2H, s), 8.07 (1H, s), 9.34 (1H, s); Mass spectrum: (M+H)+ 361.44.

Workup

  1. temperatureto cool to room temperature
  2. filtrationThe reaction mixture was filtered
  3. customthe filtrate evaporated to dryness
  4. customazeotroped with toluene
  5. customto give a brown gum
  6. filtrationfiltered
  7. customto remove iron residues
  8. customThe filtrate was purified by flash chromatography on silica eluting with an increasingly polar gradient of methanol/DCM (0/100 to 5/95)

Sources & evidence

ORD record
ord-85fc9d8bfb4946f2b527d174ef4996eb
Source dataset
uspto-grants-2010_09
Patent number
US07799781B2

Reaction notes

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