Ammonia → HCID 57435682, compound

HRID 645469Notes

Reaction equation

HRID 645469 reaction equation
[CH3:1][O:2][CH2:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1Br)[CH:12]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=1)[CH2:11][CH2:10]2)=[O:5].[Cu][C:32]#[N:33].N>CN1C(=O)CCC1>[CH3:1][O:2][CH2:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[C:32]#[N:33])[CH:12]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=1)[CH2:11][CH2:10]2)=[O:5]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 57435681HCID 57435681, compoundHCID 178418546HCID 178418546, compound2×

Product 1

HCID 57435682HCID 57435682, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of tert-butyl 4-[N-(5-methoxyacetamido-6-bromoindan-1-yl)-amino]benzoate (0.714 g, 1.50 mmol) in NMP (8 ml) [1-methyl-2-pyrrolidone] was added copper (I) cyanide (0.230 g, 2.55 mmol). The reaction mixture was placed in an oil-bath preheated to 140° C. and stirred at this temperature for 2 h. More copper (I) cyanide (0.100 g, 1.10 mmol) was then added and stirring was continued for a longer 3 hours. The reaction mixture was allowed to cool to room temperature, then poured into a mixture of aqueous ammonia (d=0.88, 7 ml) and ice (˜20 ml) and the resulting brown mixture was stirred at room temperature for ˜5 mm. The brown solid was collected by filtration washed with plenty of water, then suspended in dichloromethane (100 ml). The mixture was stirred at room temperature for 10 min, dried (Na2SO4), and concentrated in vacuo. Purification by column chromatography, on elution with 35% ethyl acetate in hexane, afforded an off white solid that was reprecipitated from dichloromethane-ethyl acetate/hexane: 0.328 g, (52%) m.p. 163-164° C. 1H-NMR (250 MHz, DMSO-d6, TMS) 1.50 (s, 9H, C(CH3)3), 1.85, 2.58 (2×m, 2H, indanyl 2-H), 2.89 (m, 2H, indanyl 3-H), 3.41 (s, 3H, OCH3), 4.05 (s, 2H, CH2OMe), 5.06 (m, 1H, indanyl 1-H), 6.73 (d, J=8.82 Hz, 2H, 3,5-H), 6.82 (d, J=8.37 Hz, 1H, N10—H), 7.59, 7.57 (2×s, each 1H, indanyl 4-H, 7-H), 7.66 (d, J=8.77 Hz, 2,6-H), 9.88 (s, 1H, CONH), MS (ESI, m/z) 444 {(M+Na)+, 100%}; Found: C, 68.21; H, 6.47, N, 9.81. C24H27N3O4 requires C, 68.39; H, 6.46, N, 9.97%.

Workup

  1. customThe reaction mixture was placed in an oil-bath
  2. custompreheated to 140° C.
  3. stirringstirring
  4. waitwas continued for a longer 3 hours
  5. stirringthe resulting brown mixture was stirred at room temperature for ˜5 mm
  6. filtrationThe brown solid was collected by filtration
  7. washwashed with plenty of water
  8. stirringThe mixture was stirred at room temperature for 10 min
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customPurification by column chromatography
  12. washon elution with 35% ethyl acetate in hexane
  13. customafforded an off white solid
  14. customthat was reprecipitated from dichloromethane-ethyl acetate/hexane

Sources & evidence

ORD record
ord-cc1958e9f2144cacbc862e4fbb5604a3
Source dataset
uspto-grants-2010_04
Patent number
US07705006B2

Reaction notes

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