O-Toluidine → 4-(4-Methoxy-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-N-o-tolyl-benzamide

HRID 605179Notes

Reaction equation

HRID 605179 reaction equation
[NH2:1][C:2]1[C:3]([CH3:8])=[CH:4][CH:5]=[CH:6][CH:7]=1.C[Al](C)C.C[O:14][C:15](=O)[C:16]1[CH:21]=[CH:20][C:19]([S:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[C:18]([NH:31][C:32]2[C:33]3[CH:41]=[CH:40][C:39]([CH3:42])=[N:38][C:34]=3[N:35]=[CH:36][N:37]=2)[CH:17]=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1>[CH3:30][O:29][C:26]1[CH:25]=[CH:24][C:23]([S:22][C:19]2[CH:20]=[CH:21][C:16]([C:15]([NH:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=3[CH3:8])=[O:14])=[CH:17][C:18]=2[NH:31][C:32]2[C:33]3[CH:41]=[CH:40][C:39]([CH3:42])=[N:38][C:34]=3[N:35]=[CH:36][N:37]=2)=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 7242O-ToluidineHCID 9357Potassium Sodium TartrateHCID 16682925TrimethylaluminumHCID 670403514-(4-Methoxy-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl ester

Product 1

HCID 670406384-(4-Methoxy-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-N-o-tolyl-benzamideYield 65%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of o-toluidine (0.208 mL, 1.94 mmol) in toluene (10 mL) was added AlMe3 (0.97 mL, 1.94 mmol) and the reaction mixture stirred for 30 minutes at room temperature. Then, the product from Example 148A (140 mg, 0.324 mmol) was added in one portion and the reaction mixture refluxed for 3 hours. The reaction mixture was cooled to room temperature and poured into a rapidly stirring solution of Rochelle's salt. After stirring the solution overnight at room temperature, the reaction was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over MgSO4, and concentrated under vacuum to a residue that was purified by silica gel chromatography using methanol in dichloromethane as eluent to provide the title compound (106 mg, 65%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 2.21 (s, 3H), 2.69 (s, 3H), 3.78 (s, 3H), 7.00 (d, J=8.82 Hz, 2H), 7.11-7.35 (m, 5H), 7.40 (d, J=8.82 Hz, 2H), 7.57 (d, J=8.46 Hz, 1H), 7.84 (d, J=6.99 Hz, 1H), 8.00 (s, 1H), 8.59 (s, 1H), 8.81 (d, J=8.09 Hz, 1H), 9.87 (s, 1H), 10.20 (s, 1H); MS (APCI) m/z 508 (M+H)+.

Workup

  1. temperaturethe reaction mixture refluxed for 3 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringAfter stirring the solution overnight at room temperature
  4. extractionthe reaction was extracted with ethyl acetate (3×50 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated under vacuum to a residue that
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-2bd00441017f4fcfa5ffeb9bb793938f
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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