Tetrahydrofuran → HCID 69215960, compound

HRID 1296505Notes

Reaction equation

HRID 1296505 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([Cl:18])[CH:12]=2)=[CH:6][C:3]=1[C:4]#N.[CH2:19]([Mg]Br)[CH3:20].C1C[O:26]CC1>>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([Cl:18])[CH:12]=2)=[CH:6][C:3]=1[C:4](=[O:26])[CH2:19][CH3:20]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 69212286HCID 69212286, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 69215960HCID 69215960, compoundYield 38%

Procedure

To a stirred solution of 2-amino-5-[(3-chloro-4-fluorophenyl)amino]benzonitrile (5.90 g, 22.5 mmol) in THF (120 mL) at 0° C. was slowly added ethyl magnesium bromide (80 mL, 80.0 mmol). The solution was stirred at room temperature for 2 days and quenched with 1N HCl. The resulting mixture was made alkaline with sodium bicarbonate solution (sat.) and extracted several times with ethyl acetate. The combined organic layers were dried over magnesium sulfate. Flash silica gel column separation using 20% ethyl acetate/hexane followed by trituration with ether gave 1-{2-amino-5-[(3-chloro-4-fluorophenyl)amino]phenyl}propan-1-one as a yellow solid (2.48 g, 38%). 1H NMR (DMSO-d6): δ 7.78 (s, 1H), 7.48 (d, J=2.5 Hz, 1H), 7.18 (t, J=9.1 Hz, 1H), 7.12 (dd, J=8.8, 2.6 Hz, 1H), 7.04 (s, 2H), 6.81 (m, 1H), 6.79 (d, J=8.8 Hz, 1H), 6.73 (m, 1H), 2.93 (q, J=7.2 Hz, 2H), 1.07 (t, J=7.1 Hz, 3H); MS (ESI) m/z 293/295 ([M+H]+); MS (ESI) m/z 291/293 ([M−H]−); Anal. calcd for C15H14ClFN2O: C, 61.54H, 4.82; N, 9.57. Found: C, 61.55; H, 4.68; N, 9.47.

Workup

  1. customat 0° C.
  2. customquenched with 1N HCl
  3. extractionextracted several times with ethyl acetate
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. customFlash silica gel column separation

Sources & evidence

ORD record
ord-2152395b54204a17a0445dc9fadf2829
Source dataset
uspto-grants-2007_07
Patent number
US07247625B2

Reaction notes

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