18-Crown-6 → tert-butyl 4-{1-(2-tetrahydropyranyl)-1H-indazol-5-ylamino}benzoate

HRID 1269892

반응식

HRID 1269892 반응식
Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.C1OCCOCCOCCOCCOCCOC1.[O:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH:34]1[N:39]1[C:47]2[C:42](=[CH:43][C:44]([NH2:48])=[CH:45][CH:46]=2)[CH:41]=[N:40]1.C(NC1C(C)=CC(C(OC)=O)=C(C)C=1)(=O)C.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(OCC)C.C1(C)C=CC=CC=1>[O:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH:34]1[N:39]1[C:47]2[C:42](=[CH:43][C:44]([NH:48][C:2]3[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=3)=[CH:45][CH:46]=2)[CH:41]=[N:40]1

참가 물질

9

반응물 6

HCID 2855718-Crown-6HCID 327521Methyl 4-acetamido-2,5-dimethylbenzoateHCID 634876Binap, (A+-)-HCID 11334366Tert-butyl 4-bromobenzoateHCID 229339271-(Oxan-2-yl)-1H-indazol-5-amineHCID 23676156Sodium t-butoxide

생성물 1

HCID 69433104tert-butyl 4-{1-(2-tetrahydropyranyl)-1H-indazol-5-ylamino}benzoate수율 56%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 3283Diethyl Ether용매

실험 절차

In a two-necked flask the inner atmosphere of which had been replaced with nitrogen were placed tert-butyl 4-bromobenzoate (2.57 mg, 1.00 mmol), toluene (2 ml), 18-crown-6 (380 mg, 1.40 mmol), the 1-(2-tetrahydropyranyl)-1H-indazol-5-amine (261 mg, 1.23 mmol) obtained in Example 317, (e) and sodium tert-butoxide (135 mg, 1.40 mmol) in that order. After the inner atmosphere of the flask was replaced with nitrogen again, tris(dibenzylideneacetone)(chloroform) dipalladium(0) (52 mg, 0.050 mmol) and (S)-2,2′-bis(diphenylphophino)-1,1′-binaphthyl (94 mg, 0.151 mmol) were added. After the third replacement of the inner atmosphere of the flask with nitrogen, stirring was conducted at 80° C. for 8 hours. The resulting mixture was diluted with diethyl ether and the solid was removed by filtration using Celite. Then, the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1) to obtain tert-butyl 4-{1-(2-tetrahydropyranyl)-1H-indazol-5-ylamino}benzoate (218 mg, 56%).

후처리

  1. customIn a two-necked flask the inner atmosphere of which had been replaced with nitrogen
  2. customthe solid was removed by filtration
  3. distillationThen, the solvent was distilled off under reduced pressure
  4. customto obtain a crude product
  5. customThe crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1)

출처 및 근거

ORD 기록
ord-7171331d452549a1932e5a6d8ccbf5ae
출처 데이터셋
uspto-grants-2007_04
특허 번호
US07199147B2

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