Tetrahydrofuran → HCID 11677831, compound

HRID 1811577Notes

Reaction equation

HRID 1811577 reaction equation
[CH2:1]([CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[C:21]([O:22][CH3:23])=[C:20](Cl)[N:19]=[CH:18][N:17]=2)[CH2:11][CH2:10]1)=[O:8])[CH2:4][CH3:5])[CH3:2].[CH3:25][S:26]([C:29]1[N:34]=[C:33]([CH3:35])[C:32]([NH2:36])=[CH:31][CH:30]=1)(=[O:28])=[O:27].C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.CC(C)([O-])C.[K+].C1COCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[C:21]([O:22][CH3:23])=[C:20]([NH:36][C:32]3[C:33]([CH3:35])=[N:34][C:29]([S:26]([CH3:25])(=[O:28])=[O:27])=[CH:30][CH:31]=3)[N:19]=[CH:18][N:17]=2)[CH2:11][CH2:10]1)=[O:8])[CH2:4][CH3:5])[CH3:2]

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneHCID 23665647Potassium tert-butoxideHCID 510505272-Methyl-6-(methylsulfonyl)pyridin-3-amineHCID 86606453HCID 86606453, compound

Product 1

HCID 11677831HCID 11677831, compoundYield 2.11%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

4-(6-Chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid 1-ethyl-propyl ester, (0.50 g, 1.40 mmol) and 6-methanesulfonyl-2-methyl-pyridin-3-ylamine (0.26 g, 1.40 mmol) and palladium acetate (0.062 g, 0.28 mmol) and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (0.191 g, 0.559 mmol) were combined in 50 mL dioxane, purged with nitrogen and a 1M solution of potassium t-butoxide in THF (2.79 mL, 2.79 mmol) added dropwise. The reaction was heated to 100° C. and stirred for 2 hours, then was filtered, concentrated, acidified and purified by prep HPLC, the desired fractions partitioned between saturated sodium hydrogen carbonate and ethyl acetate, the organic phase washed with brine and dried with magnesium sulfate to yield (15 mg, 0.029 mmol, 2.11% yield) desired product, as a white solid. 1HNMR (CDCl3, 400 MHz) δ 0.91 (t, J=7.33 Hz, 6H), 1.54-1.64 (m, 4H), 1.77-1.87 (m, 2H), 1.99-2.08 (m, 2H), 2.65 (s, 3H), 3.19 (s, 3H), 3.39-3.46 (m, 2H), 3.78-3.85 (m, 2H), 4.00 (s, 3H), 4.67 (pent, J=6.32 Hz, 1H), 5.36-5.43 (hept, J=3.79 Hz, 1H), 7.31 (bs, 1H), 7.96 (d, J=8.34 Hz, 1H), 8.20 (s, 1H), 9.02 (d, J=8.59 Hz, 1H). Exact mass calculated for C23H33N5O6S: 507.22 found: 508.5 (MH+).

Workup

  1. custompurged with nitrogen
  2. filtrationwas filtered
  3. concentrationconcentrated
  4. custompurified by prep HPLC
  5. customthe desired fractions partitioned between saturated sodium hydrogen carbonate and ethyl acetate
  6. washthe organic phase washed with brine
  7. dry with materialdried with magnesium sulfate

Sources & evidence

ORD record
ord-b71767844f084661af093a40344718d8
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

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