(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamide → {4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 605061Notes

Reaction equation

HRID 605061 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:42])[NH:17][C:18]3[CH:23]=[CH:22][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:40])[NH:32][C:33]5[CH:38]=[CH:37][C:36]([Br:39])=[CH:35][N:34]=5)=[CH:27][C:26]=4[NH2:41])=[CH:20][CH:19]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C([C:45]1[C:46]([N:54]=[CH:55][N:56]([CH3:58])C)=[N:47][C:48]([CH:51]([CH3:53])[CH3:52])=[CH:49][CH:50]=1)#N>C(O)(=O)C>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:42])[NH:17][C:18]3[CH:19]=[CH:20][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:40])[NH:32][C:33]5[CH:38]=[CH:37][C:36]([Br:39])=[CH:35][N:34]=5)=[CH:27][C:26]=4[NH:41][C:58]4[C:45]5[CH:50]=[CH:49][C:48]([CH:51]([CH3:52])[CH3:53])=[N:47][C:46]=5[N:54]=[CH:55][N:56]=4)=[CH:22][CH:23]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 66808369(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamideHCID 67040714{4-[2-Amino-4-(5-bromo-pyridin-2-ylcarbamoyl)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 67040609{4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl esterYield 58.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of the product from Example 17D (23.9 g, 37.4 mmol) and N′-(3-cyano-6-isopropyl-pyridin-2-yl)-N,N-dimethyl-formamidine (9.71 g, 44.9 mmol, 1.2 eq) in 450 mL of glacial acetic acid was heated in an oil bath at 150° C. for 2 h and then cooled to room temperature. The reaction mixture was evaporated in vacuo and the residue was dissolved in approximately 70 mL of dichloromethane. This material was purified by silica gel chromatography using a Biotage Flash 75M cartridge, eluting first with 1:4 ethyl acetate/dichloromethane followed by 98:2 dichloromethane/methanol. The resulting product triturated with dichloromethane and filtered to provide the title compound as a white solid (17.6 g, 58%).

Workup

  1. temperaturecooled to room temperature
  2. customThe reaction mixture was evaporated in vacuo
  3. dissolutionthe residue was dissolved in approximately 70 mL of dichloromethane
  4. customThis material was purified by silica gel chromatography
  5. washeluting first with 1:4 ethyl acetate/dichloromethane
  6. customThe resulting product triturated with dichloromethane
  7. filtrationfiltered

Sources & evidence

ORD record
ord-2fa67cb2020146cb9cc6dbc01988a0b8
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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