Methane → 3-(2''-Aminotrispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-6'-yl)pyridine-2-carbonitrile

HRID 594906ノート

反応式

HRID 594906 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:17]3([CH2:21][O:20][C:19]([N:22](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:18]3)[C:13]3([CH2:16][O:15][CH2:14]3)[C:9]3([CH2:12][CH2:11][CH2:10]3)[O:8][C:5]2=[CH:6][CH:7]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].Br[C:61]1[C:62]([C:67]#[N:68])=[N:63][CH:64]=[CH:65][CH:66]=1.C([O-])([O-])=O.[Na+].[Na+].C>O1CCOCC1.C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:22][C:19]1[O:20][CH2:21][C:17]2([C:13]3([CH2:14][O:15][CH2:16]3)[C:9]3([CH2:12][CH2:11][CH2:10]3)[O:8][C:5]3[C:4]2=[CH:3][C:2]([C:61]2[C:62]([C:67]#[N:68])=[N:63][CH:64]=[CH:65][CH:66]=2)=[CH:7][CH:6]=3)[N:18]=1

参加物

11

反応物 6

HCID 297MethaneHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 8176943-Bromopyridine-2-carbonitrileHCID 2733548Bis(pinacolato)diboraneHCID 86724300Di-tert-butyl (6'-bromotrispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-yl)imidodicarbonate

生成物 1

HCID 900256583-(2''-Aminotrispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-6'-yl)pyridine-2-carbonitrile収率 68.4%

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of di-tert-butyl (6′-bromotrispiro[cyclobutane-1,2′-chromene-4′,4″-[1,3]oxazole-3′,3′″-oxetan]-2″-yl)imidodicarbonate (300 mg, 0.531 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (150 mg, 0.584 mmol), potassium acetate (91.1 mg, 0.928 mmol) and bis(triphenylphosphine)palladium(II) dichloride (37 mg, 0.053 mmol) in dioxane (2.4 mL) was stirred for 7 hours at 100° C. To the mixture was added 3-bromo-2-cyanopyridine (243 mg, 1.33 mmol), Na2CO3 (225 mg, 2.12 mmol) and water (0.60 mL), and the mixture was stirred for 2 hours at 100° C. The mixture was treated with charcoal, and filtered off. The filtrate was partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered, and the filtrate was evaporated to give a pale brown oil. The oil was dissolved in toluene (3.0 mL) and to the mixture was added silica gel (neutral; 900 mg). The mixture was refluxed for 1 hour. The solvent was evaporated off. Silica gel column chromatography (CHCl3-EtOH, a linear gradient of EtOH from 0 to 10%) afforded a solid. The solid was triturated in Et2O, collected by filtration, washed with Et2O and dried at reduced pressure at 70° C. to give 3-(2″-aminotrispiro[cyclobutane-1,2′-chromene-4′,4″-[1,3]oxazole-3′,3′″-oxetan]-6′-yl)pyridine-2-carbonitrile (141 mg).

後処理

  1. stirringthe mixture was stirred for 2 hours at 100° C
  2. filtrationfiltered off
  3. customThe filtrate was partitioned between EtOAc and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe filtrate was evaporated
  8. customto give a pale brown oil
  9. additionwas added silica gel (neutral; 900 mg)
  10. temperatureThe mixture was refluxed for 1 hour
  11. customThe solvent was evaporated off
  12. customSilica gel column chromatography (CHCl3-EtOH, a linear gradient of EtOH from 0 to 10%) afforded a solid
  13. customThe solid was triturated in Et2O
  14. filtrationcollected by filtration
  15. washwashed with Et2O
  16. customdried at reduced pressure at 70° C.

出典と根拠

ORDレコード
ord-aafecc7884504b97a3e05206c23a1368
出典データセット
uspto-grants-2016_01
特許番号
US09242973B2

反応ノート

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