2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → HCID 11648576, compound

HRID 1811570Notes

Reaction equation

HRID 1811570 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[CH3:23][C:24]1[C:29]([NH2:30])=[CH:28][CH:27]=[C:26]([S:31][CH2:32][CH2:33][CH3:34])[N:25]=1.C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.CC([O-])(C)C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:30][C:29]3[C:24]([CH3:23])=[N:25][C:26]([S:31][CH2:32][CH2:33][CH3:34])=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneHCID 23676156Sodium t-butoxideHCID 51050526Isopropyl 4-[(6-chloro-5-methoxypyrimidin-4-yl)oxy]piperidine-1-carboxylateHCID 58671590HCID 58671590, compound

Product 1

HCID 11648576HCID 11648576, compoundYield 36.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(6-chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (0.966 g, 2.93 mmol), 2-methyl-6-propylsulfanyl-pyridin-3-ylamine (0.545 g, 2.99 mmol), palladium acetate (0.0375 g, 0.167 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (0.119 mL, 0.335 mmol), and sodium 2-methylpropan-2-olate (0.422 g, 4.39 mmol) in 15 mL dioxane was heated under microwave irradiation at 120° C. After 2 h, mixture was purified by HPLC; fractions containing pure product were collected, partly concentrated, and residue was extracted with CH2Cl2 and 1M NaOH. Organic phases were dried over MgSO4, filtered, and concentrated to give 4-[5-methoxy-6-(2-methyl-6-propylsulfanyl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester as a thick oil (0.509 g, 36%). 1HNMR (MeOH-d4, 400 MHz) δ 1.00-1.04 (t, J=7.3 Hz, 3H), 1.23-1.24 (d, J=6.2 Hz, 6H), 1.66-1.78 (m, 4H), 1.96-2.02 (m, 2H), 2.37 (s, 3H), 3.06-3.10 (t, J=7.3 Hz, 2H), 3.36-3.42 (m, 2H), 3.71-3.77 (m, 2H), 3.88 (s, 3H), 4.81-4.87 (m, 1H), 5.28-5.34 (m, 1H), 7.09-7.11 (d, J=8.3 Hz, 1H), 7.57-7.59 (d, J=8.3 Hz, 1H), 7.84 (s, 1H). Exact mass calculated for C23H33N5O4S 475.23 found 476.1 (MH+).

Workup

  1. custommixture was purified by HPLC
  2. additionfractions containing pure product
  3. customwere collected
  4. concentrationpartly concentrated
  5. extractionresidue was extracted with CH2Cl2 and 1M NaOH
  6. dry with materialOrganic phases were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1e39b1adcffe47dcaaa704f94c8f8b74
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

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