Ammonia → Tert-butyl 4-[N-(5-acetamido-6-cyanoindan-1-yl)amino]-2-fluorobenzoate

HRID 1297522Notes

Reaction equation

HRID 1297522 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1Br)[CH:10]([NH:15][C:16]1[CH:28]=[CH:27][C:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[C:18]([F:29])[CH:17]=1)[CH2:9][CH2:8]2)(=[O:3])[CH3:2].[Cu][C:31]#[N:32].N>CN1C(=O)CCC1>[C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:31]#[N:32])[CH:10]([NH:15][C:16]1[CH:28]=[CH:27][C:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[C:18]([F:29])[CH:17]=1)[CH2:9][CH2:8]2)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 58915010tert-butyl 4-[N-(5-acetamido-6-bromoindan-1-yl)amino]-2-fluorobenzoateHCID 178418546HCID 178418546, compound

Product 1

HCID 67363698Tert-butyl 4-[N-(5-acetamido-6-cyanoindan-1-yl)amino]-2-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of tert-butyl 4-[N-(5-acetamido-6-bromoindan-1-yl)amino]-2-fluorobenzoate (0.420 g, 0.90 mmol) in NMP (10 ml) was added copper(I) cyanide (0.137 g, 1.53 mmol). The reaction mixture was placed in an oil-bath preheated to 145° C. and stirred at this temperature for 2 hours. The reaction mixture was allowed to cool to room temperature, then poured into a mixture of aqueous ammonia (d=0.88, 5 ml) and ice (˜15 ml) and the resulting brown mixture was stirred at room temperature for ˜5 min. The brown solid was collected by filtration washed with water, then suspended in dichloromethane (60 ml). The mixture was stirred at room temperature for 5 min, dried (Na2SO4), and concentrated in vacuo. Purification by column chromatography, on elution with 40% ethyl acetate in hexane, afforded a solid that was triturated with diethyl ether/hexane. The desired compound was obtained as a white solid: 0.202 g, (55%) m.p. 172-173° C.; 1H-NMR (250 MHz, CDCl3, TMS) 1.57 (s (obscured by water peak), 9H, C(CH3)3), 2.27 (s, 3H, COCH3), 1.96, 2.65 (2×m, 2H, indanyl 2-H), 3.00 (m, 2H, indanyl 3-H), 4.30 (d, J=8.40 Hz, 1H, N-H), 4.99 (q, J=7.80 Hz, 1H, indanyl 1-H), 6.38 (m, 2H, 3,5-H), 7.52, 8.33, 7.62 (3×s, each 1H, indanyl 4-H, 7-H, CONH), 7.74 (t, J=8.60 Hz, 1H, 6-H); MS (ESI m/z) 432 {M+Na)+, 100%}; Found: C, 67.44; H, 5.88; N, 10.25; F, 4.63; C23H24FN3O3 requires C, 67.47; H, 5.91; N, 10.26%; F, 4.64%.

Workup

  1. customThe reaction mixture was placed in an oil-bath
  2. custompreheated to 145° C.
  3. stirringthe resulting brown mixture was stirred at room temperature for ˜5 min
  4. filtrationThe brown solid was collected by filtration
  5. washwashed with water
  6. stirringThe mixture was stirred at room temperature for 5 min
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography
  10. washon elution with 40% ethyl acetate in hexane
  11. customafforded a solid
  12. customthat was triturated with diethyl ether/hexane

Sources & evidence

ORD record
ord-4682f14794a64342abc5feb11d975cbc
Source dataset
uspto-grants-2007_07
Patent number
US07250511B2

Reaction notes

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