Cesium carbonate → HCID 11526494, compound

HRID 1811592Notes

Reaction equation

HRID 1811592 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[C:3]=1[O:21][CH3:22].[CH3:23][C:24]1[C:29]([NH2:30])=[CH:28][CH:27]=[C:26]([C:31]([S:34]([CH3:37])(=[O:36])=[O:35])([CH3:33])[CH3:32])[N:25]=1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[CH3:22][O:21][C:3]1[C:4]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:5][CH:6]=[N:7][C:2]=1[NH:30][C:29]1[C:24]([CH3:23])=[N:25][C:26]([C:31]([S:34]([CH3:37])(=[O:36])=[O:35])([CH3:32])[CH3:33])=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 51050526Isopropyl 4-[(6-chloro-5-methoxypyrimidin-4-yl)oxy]piperidine-1-carboxylateHCID 58671591HCID 58671591, compound

Product 1

HCID 11526494HCID 11526494, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of isopropyl 4-(6-chloro-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate (78.5 mg, 0.238 mmol), 2-methyl-6-(2-(methylsulfonyl)propan-2-yl)pyridin-3-amine (54.3 mg, 0.238 mmol), Pd2(dba)3 (20.0 mg, 0.0218 mmol), biphenyl-2-yl-di-tert-butyl-phosphane (3.0 mg, 0.0101 μmol), and cesium carbonate (160 mg, 0.491 mmol) in 4M dioxane were heated under microwave irradiation at 100° C. Mixture was purified by HPLC; fractions containing product were partly concentrated, and residue was extracted with CH2Cl2 and 1M NaHCO3. Organic phases were dried over MgSO4, filtered, and concentrated to give isopropyl 4-(5-methoxy-6-(2-methyl-6-(2-(methylsulfonyl)propan-2-yl)pyridin-3-ylamino)pyrimidin-4-yloxy)piperidine-1-carboxylate (4.6 mg, 4%) as a white solid. 1HNMR (CDCl3, 400 MHz) δ 1.16-1.17 (d, J=6.3 Hz, 6H), 1.80-1.86 (m, 2H), 1.87 (s, 6H), 2.01-2.06 (m, 2H), 2.56 (s, 3H), 2.81 (s, 3H), 3.38-3.44 (m, 2H), 3.77-3.82 (m, 2H), 3.96 (s, 3H), 4.91-4.97 (m, 1H), 5.35-5.39 (m, 1H), 6.98 (s, 1H), 7.51-7.53 (d, J=8.6 Hz, 1H), 8.13 (s, 1H), 8.51-8.53 (d, J=8.6 Hz, 1H). Exact mass calculated for C24H35N5O6S 521.23 found 522.5 (MH+).

Workup

  1. customMixture was purified by HPLC
  2. additionfractions containing product
  3. concentrationwere partly concentrated
  4. extractionresidue was extracted with CH2Cl2 and 1M NaHCO3
  5. dry with materialOrganic phases were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-21a40bc129e94113a9b2bfac886a6620
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

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