Sodium Hydroxide → tert-butyl [(1S,2R)-2-({6-carbamoyl-5-[(5-hydroxy-6-methylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate

HRID 1504757Notes

Reaction equation

HRID 1504757 reaction equation
[OH-:1].[Na+].Br[C:4]1[CH:5]=[CH:6][C:7]([NH:11][C:12]2[CH:13]=[C:14]([NH:20][C@@H:21]3[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]3[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:15]=[N:16][C:17]=2[C:18]#[N:19])=[N:8][C:9]=1[CH3:10].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[O:69]1CCOCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:18]([C:17]1[N:16]=[CH:15][C:14]([NH:20][C@@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]2[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:13][C:12]=1[NH:11][C:7]1[CH:6]=[CH:5][C:4]([OH:69])=[C:9]([CH3:10])[N:8]=1)(=[O:1])[NH2:19]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 86731651tert-butyl (1S,2R)-2-(5-(5-bromo-6-methylpyridin-2-ylamino)-6-cyanopyridin-3-ylamino)cyclohexylcarbamate

Product 1

HCID 86731654tert-butyl [(1S,2R)-2-({6-carbamoyl-5-[(5-hydroxy-6-methylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

This example describes the conversion of (B9) to (C11) shown in Scheme 2. Dioxane (2.40 mL) and sodium hydroxide (4.0 N in water, 0.36 mL, 1.4 mmol) were added to tert-butyl [(1S,2R)-2-({5-[(5-bromo-6-methylpyridin-2-yl)amino]-6-cyanopyridin-3-yl}amino)cyclohexyl]carbamate (PrepEx 1.6) (0.241 g, 0.481 mmol) in a scintillation vial. The vial was purged and flushed with argon three times before Pd2(dba)3 (0.013 g, 0.014 mmol) and 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-tri-isopropylbiphenyl (0.028 g, 0.058 mmol) were added. The vial was purged and flushed three times with argon before the vial was sealed and heated to 80° C. After 4 hours, the reaction was cooled to room temperature, filtered through CELITE (washed with dichloromethane) and diluted with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% acetone/hexanes, linear gradient) to afford tert-butyl [(1S,2R)-2-({6-carbamoyl-5-[(5-hydroxy-6-methylpyridin-2-yl)amino]pyridin-3-yl}amino)cyclohexyl]carbamate. MS ESI calc'd. for C23H33N6O4 [M+H]+ 457. found 457.

Workup

  1. customThe vial was purged
  2. additionwere added
  3. customThe vial was purged
  4. customflushed three times with argon before the vial
  5. customwas sealed
  6. temperaturethe reaction was cooled to room temperature
  7. filtrationfiltered through CELITE (washed with dichloromethane)
  8. additiondiluted with water
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel chromatography (0-100% acetone/hexanes, linear gradient)

Sources & evidence

ORD record
ord-5aae18373070410dafa0131bf680db33
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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