(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamide → {4-[4-(4-Bromo-phenylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenoxy]-phenyl}-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 605321Notes

Reaction equation

HRID 605321 reaction equation
[Cl:1][C:2]([Cl:33])([Cl:32])[CH2:3][O:4][C:5](=[O:31])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=3)=[CH:16][C:15]=2[NH2:30])=[CH:9][CH:8]=1.C([C:36]1[C:37]([N:45]=[CH:46][N:47]([CH3:49])C)=[N:38][C:39]([CH:42]([CH3:44])[CH3:43])=[CH:40][CH:41]=1)#N>C(O)(=O)C>[Cl:33][C:2]([Cl:1])([Cl:32])[CH2:3][O:4][C:5](=[O:31])[NH:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=3)=[CH:16][C:15]=2[NH:30][C:49]2[C:36]3[CH:41]=[CH:40][C:39]([CH:42]([CH3:43])[CH3:44])=[N:38][C:37]=3[N:45]=[CH:46][N:47]=2)=[CH:11][CH:12]=1

Participants

4

Reactant 2

HCID 66808369(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamideHCID 67040452{4-[2-Amino-4-(4-bromo-phenylcarbamoyl)-phenoxy]-phenyl}-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 67040172{4-[4-(4-Bromo-phenylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenoxy]-phenyl}-carbamic acid 2,2,2-trichloro-ethyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of the products of Example 361E (2.39 g, 4.2 mmol) and Example 8E (N′-(3-cyano-6-isopropyl-pyridin-2-yl)-N,N-dimethyl-formamidine) (0.91 g, 4.2 mmol) in 10 mL of glacial acetic acid was heated in a 140° C. preheated oil bath for 45 minutes. The reaction mixture was cooled, evaporated in vacuo and the residue partitioned between ethyl acetate (250 mL) and water (100 mL). The organic phase was then washed with saturated aqueous sodium bicarbonate and then brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The resulting residue was triturated with methanol, filtered, and dried in vacuo to provide the title compound (2.0 g, 64%) as a beige solid. MS (ESI+) m/z 743/745 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.31 (d, J=6.62 Hz, 6 H), 3.10-3.27 (m, 1 H), 4.93 (s, 2 H), 6.93-7.05 (m, 3 H), 7.39-7.62 (m, 5 H), 7.77 (d, J=8.82 Hz, 2 H), 8.17 (s, 1 H), 8.60 (s, 1 H), 8.78 (d, J=8.09 Hz, 1 H), 10.08 (s, 1 H), 10.16 (s, 1 H), 10.35 (s, 2 H).

Workup

  1. customfor 45 minutes
  2. temperatureThe reaction mixture was cooled
  3. customevaporated in vacuo
  4. customthe residue partitioned between ethyl acetate (250 mL) and water (100 mL)
  5. washThe organic phase was then washed with saturated aqueous sodium bicarbonate
  6. dry with materialbrine, dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe resulting residue was triturated with methanol
  10. filtrationfiltered
  11. customdried in vacuo

Sources & evidence

ORD record
ord-ef774315c71c40438aaf0e13163ce33e
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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