Carbamate → HCID 18357730, compound

HRID 427737Notes

Reaction equation

HRID 427737 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH3:16])[C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)=[N:6][CH:7]=1.Cl[C:18](OC1C=CC=CC=1)=O.[C:27](=[O:30])([O-])[NH2:28].CO[C:33]1[C:34]([C:45]([F:48])([F:47])[F:46])=[CH:35][C:36]([N+]([O-])=O)=[C:37]([CH2:39][C:40]#N)[CH:38]=1>ClCCl.CN(C=O)C.CO.ClCCl.C(N(CC)CC)C>[CH3:18][C:33]1[CH:38]=[C:37]2[C:36](=[CH:35][C:34]=1[C:45]([F:48])([F:47])[F:46])[N:28]([C:27](=[O:30])[NH:1][C:2]1[CH:3]=[C:4]([CH3:16])[C:5]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)=[N:6][CH:7]=1)[CH2:40][CH2:39]2

Participants

9

Reactant 4

HCID 276CarbamateHCID 15891Phenyl chloroformateHCID 107777195-Methoxy-2-nitro-4-(trifluoromethyl)benzene acetonitrileHCID 183577225-Amino-3-methyl-2(pyridin-2-ylmethyloxy)pyridine

Product 1

HCID 18357730HCID 18357730, compoundYield 28%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

5-Amino-3-methyl-2(pyridin-2-ylmethyloxy)pyridine (D15, 0.5 g, 2.3 mmol) in dichloromethane (30 ml) was cooled to −20° C. under argon. Triethylamine (0.32 ml, 2.3 mmol) was added, followed dropwise by phenyl chloroformate (0.35 ml, 2.8 mmol). The mixture was warmed to room temperature and diluted with dichloromethane (100 ml) then washed with aqueous sodium bicarbonate (50 ml), dried (Na2SO4) and evaporated in vacuo to give phenyl N-2-[3-methyl-(pyridin-2-ylmethyloxypyridin-5-yl]carbamate. The crude carbamate was treated with 5-methyl-6-trifluoromethylindoline (D7, 0.47 g, 0.0023 mol, 1 eq) and triethylamine (1 ml) in DMF (30 ml) at 100° C. under argon for 2 hours then allowed to cool. Solvent was removed in vacuo and the residue was partitioned between dichloromethane (3×100 ml) and 10% aqueous sodium hydroxide (50 ml). The combined organics were dried (Na2SO4) and evaporated in vacuo to give the crude product which was subjected to flash chromatography using 5% methanol/dichloromethane as eluant and recrystallised from dichloromethane/60-80° C. petroleum ether to afford the title compound (0.27 g, 28%) as white crystals. m.p. 188-189° C.

Workup

  1. washthen washed with aqueous sodium bicarbonate (50 ml)
  2. dry with materialdried (Na2SO4)
  3. customevaporated in vacuo
  4. customto give phenyl N-2-[3-methyl-(pyridin-2-ylmethyloxypyridin-5-yl]carbamate
  5. temperatureto cool
  6. customSolvent was removed in vacuo
  7. customthe residue was partitioned between dichloromethane (3×100 ml) and 10% aqueous sodium hydroxide (50 ml)
  8. dry with materialThe combined organics were dried (Na2SO4)
  9. customevaporated in vacuo
  10. customto give the crude product which
  11. customrecrystallised from dichloromethane/60-80° C. petroleum ether

Sources & evidence

ORD record
ord-0e3303ad32ac4c58b69515ab2db75dbc
Source dataset
uspto-grants-2001_11
Patent number
US06313145B1

Reaction notes

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