4-Amino-1-Boc-piperidine → 4-[4-(4-Chloro-benzyl)-6-(1-hydroxy-1-methyl-ethyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 451420Notes

Reaction equation

HRID 451420 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[N:3]=1.[NH2:20][CH:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:30]([O:29][C:27]([N:24]1[CH2:25][CH2:26][CH:21]([NH:20][C:2]2[N:3]=[C:4]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)[CH:5]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[N:7]=2)[CH2:22][CH2:23]1)=[O:28])([CH3:33])([CH3:31])[CH3:32]

Participants

8

Reactant 4

HCID 12682914-Amino-1-Boc-piperidineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 866567012-[2-Chloro-6-(4-chloro-benzyl)-pyrimidin-4-yl]-propan-2-ol

Product 1

HCID 673420264-[4-(4-Chloro-benzyl)-6-(1-hydroxy-1-methyl-ethyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl esterYield 30%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a mixture of 2-[2-chloro-6-(4-chloro-benzyl)-pyrimidin-4-yl]-propan-2-ol (500 mg, 1.68 mmol), 4-amino-1-Boc-piperidine (404 mg, 2.02 mmol), sodium tert-butoxide (243 mg, 2.52 mmol) in dioxane (2.5 mL) was added under an argon atmosphere palladium(II) acetate (30 mg, 0.14 mmol) and 2-(dicyclohexylphosphino)biphenyl (94 mg, 0.27 mmol) and the reaction mixture was heated to 150° C. for 30 minutes in a microwave oven. It was diluted with ethyl acetate (15 mL) and washed with water (15 mL) and brine (15 mL). The aqueous layers were extracted with ethyl acetate (15 mL) and dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate=80:20 to 60:40) afforded the title compound (230 mg, 30%) as a light brown oil.

Workup

  1. washwashed with water (15 mL) and brine (15 mL)
  2. extractionThe aqueous layers were extracted with ethyl acetate (15 mL)
  3. dry with materialdried over sodium sulfate
  4. customPurification by chromatography (SiO2, heptane:ethyl acetate=80:20 to 60:40)

Sources & evidence

ORD record
ord-3c52f781cb2a42398c98fcbaf3de2e7f
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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