Potassium Phosphate, Tribasic → tert-butyl (1S,2R)-2-(6-cyano-5-(6-methyl-4-phenylpyridin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate

HRID 1504864Notes

Reaction equation

HRID 1504864 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl[C:19]1[CH:24]=[C:23]([CH3:25])[N:22]=[C:21]([NH:26][C:27]2[CH:28]=[C:29]([NH:35][C@@H:36]3[CH2:41][CH2:40][CH2:39][CH2:38][C@@H:37]3[NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH:30]=[N:31][C:32]=2[C:33]#[N:34])[CH:20]=1>C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].C(Cl)Cl.O1CCOCC1>[C:33]([C:32]1[N:31]=[CH:30][C:29]([NH:35][C@@H:36]2[CH2:41][CH2:40][CH2:39][CH2:38][C@@H:37]2[NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[CH:28][C:27]=1[NH:26][C:21]1[CH:20]=[C:19]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:24]=[C:23]([CH3:25])[N:22]=1)#[N:34]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 86731656tert-butyl (1S,2R)-2-(5-(4-chloro-6-methylpyridin-2-ylamino)-6-cyanopyridin-3-ylamino)cyclohexylcarbamate

Product 1

HCID 86731732tert-butyl (1S,2R)-2-(6-cyano-5-(6-methyl-4-phenylpyridin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate

Reagents, catalysts & solvents 2

HCID 178478472(1,1'-Bis(diphenylphosphino)ferrocene)dichloropalladium-dichloromethane (1:1)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Dioxane (1.1 mL), phenylboronic acid (27 mg, 0.22 mmol), and potassium phosphate tribasic (70 mg, 0.33 mmol) were added to a nitrogen purged flask containing tert-butyl [(1S,2R)-2-({5-[(4-chloro-6-methylpyridin-2-yl)amino]-6-cyanopyridin-3-yl}amino)cyclohexyl]carbamate (PrepEx 1.7) (50 mg, 0.11 mmol). The flask was purged and flushed with nitrogen, and then PdCl2(dPPf)-CH2Cl2 (9 mg, 0.01 mmol) was added. The flask was purged with nitrogen, sealed, and heated to 90° C. for 2 hours. The reaction mixture was cooled to room temperature, diluted with 10% aqueous sodium bicarbonate (10 mL) and extracted with ethyl acetate (10 mL). The organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (10-50% ethyl acetate/hexanes, linear gradient) to afford tert-butyl (1S,2R)-2-(6-cyano-5-(6-methyl-4-phenylpyridin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate. MS ESI calc'd. for C29H35N6O2 [M+H]+ 499. found 499.

Workup

  1. customThe flask was purged
  2. customflushed with nitrogen
  3. customThe flask was purged with nitrogen
  4. customsealed
  5. temperatureThe reaction mixture was cooled to room temperature
  6. additiondiluted with 10% aqueous sodium bicarbonate (10 mL)
  7. extractionextracted with ethyl acetate (10 mL)
  8. dry with materialThe organics were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by chromatography on silica gel (10-50% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-678453c061ce4447b8ee1fe32598ab53
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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