2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → Hydrochloric Acid

HRID 1811583Notes

Reaction equation

HRID 1811583 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]3[O:21][N:20]=[C:19]([CH:22]([CH3:24])[CH3:23])[N:18]=3)[CH2:13][CH2:12]2)[N:5]=[CH:4][N:3]=1.[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.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:22]([C:19]1[N:18]=[C:17]([N:14]2[CH2:15][CH2:16][CH:11]([O:10][C:6]3[N:5]=[CH:4][N:3]=[C:2]([NH:36][C:32]4[C:33]([CH3:35])=[N:34][C:29]([S:26]([CH3:25])(=[O:28])=[O:27])=[CH:30][CH:31]=4)[C:7]=3[O:8][CH3:9])[CH2:12][CH2:13]2)[O:21][N:20]=1)([CH3:24])[CH3:23].[ClH:1]

Participants

8

Reactant 4

HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneHCID 23676156Sodium t-butoxideHCID 510505272-Methyl-6-(methylsulfonyl)pyridin-3-amineHCID 586715644-Chloro-5-methoxy-6-[[1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl]oxy]pyrimidine

Product 2

HCID 313Hydrochloric AcidHCID 58671592HCID 58671592, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
150 °C

Procedure

A mixture of 4-chloro-6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-5-methoxy-pyrimidine (1.78 g, 5.03 mmol), 6-Methanesulfonyl-2-methyl-pyridin-3-ylamine (1.12 g, 6.04 mmol), palladium acetate (102 mg, 0.45 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (322 μl, 0.91 mmol) and sodium tert-butoxide (725 mg, 7.54 mmol) in 30 mL of dioxane was heated under microwave irradiation at 150° C. for 1 hr. Additional 40 mL of dioxane were added and the mixture was refluxed under 130° C. After 65 hr, mixture was purified by HPLC. Fractions with product were collected, concentrated, and recrystalized with hot ethanol. 4N HCl in dioxane (ca 1 mL) and acetonitrile (ca 3 mL) were added and concentrated to give {6-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-5-methoxy-pyrimidin-4-yl}-(6-methanesulfonyl-2-methyl-pyridin-3-yl)-amine as white solid (HCl salt, 360 mg, 13.3%). 1HNMR (DMSO-d6, 400 MHz) δ 1.19-1.21 (d, J=6.82 Hz, 6H), 1.83-1.85 (m, 2H), 2.06-2.08 (m, 2H), 2.51 (s, 3H), 2.81-2.84 (sept, J=6.82 Hz, 1H), 3.57-3.59 (m, 2H), 3.75-3.77 (m, 2H), 3.87 (s, 1H), 5.31-3.39 (m, 1H), 7.89-7.91 (d, J=8.34 Hz, 1H), 8.07 (s, 1H), 8.23-8.25 (d, J=8.34 Hz, 1H) 8.69 (s, 1H). Exact mass calculated for C22H29N7O5S 503.2 found 504.2 (MH+).

Workup

  1. temperaturethe mixture was refluxed under 130° C
  2. custommixture was purified by HPLC
  3. customFractions with product were collected
  4. concentrationconcentrated
  5. customrecrystalized with hot ethanol
  6. addition4N HCl in dioxane (ca 1 mL) and acetonitrile (ca 3 mL) were added
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-164c9281ffa74200a5b41279d5c7e2d0
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

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