Acrylonitrile → (+/-)-trans-3-{[3-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]amino}cyclohexyl]-oxy}propanenitrile

HRID 2189049Notes

Reaction equation

HRID 2189049 reaction equation
CC(C)([O-])C.[K+].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:23]3[C:22]([NH:24][C@H:25]4[CH2:30][CH2:29][CH2:28][C@H:27]([OH:31])[CH2:26]4)=[N:21][CH:20]=[N:19][C:18]=3[O:17][C:16]=2[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:11][CH:10]=1.[C:38](#[N:41])[CH:39]=[CH2:40]>C1COCC1.ClCCl>[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:23]3[C:22]([NH:24][C@H:25]4[CH2:30][CH2:29][CH2:28][C@H:27]([O:31][CH2:40][CH2:39][C:38]#[N:41])[CH2:26]4)=[N:21][CH:20]=[N:19][C:18]=3[O:17][C:16]=2[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 7855AcrylonitrileHCID 23665647Potassium tert-butoxideHCID 58280259trans-3-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]amino}cyclohexanol

Product 1

HCID 58280115(+/-)-trans-3-{[3-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]amino}cyclohexyl]-oxy}propanenitrile

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add a solution of approx. 2 mg of potassium tert-butoxide in 0.2 ml of THF dropwise to a solution of 34.4 mg (0.059 mmol) of (+/−)-trans-3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]amino}cyclohexanol in 0.23 ml of acrylonitrile. Stir the reaction mixture with exclusion of light at RT for approx. 2 h. After diluting with dichloromethane, wash successively with 1N hydrochloric acid, satd. sodium hydrogencarbonate solution and satd. sodium chloride solution, and concentrate the organic phase under reduced pressure. After the residue has been purified by means of preparative RP-HPLC (eluent: acetonitrile/water gradient), 33.6 mg of the target product are obtained (86.6% of theory).

Workup

  1. washwash successively with 1N hydrochloric acid
  2. concentrationsodium chloride solution, and concentrate the organic phase under reduced pressure
  3. customAfter the residue has been purified by means of preparative RP-HPLC (eluent: acetonitrile/water gradient), 33.6 mg of the target product
  4. customare obtained (86.6% of theory)

Sources & evidence

ORD record
ord-25c7042d9b374561af9c6b6abab5c0b8
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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