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Sodium Bicarbonate → 1,1-dimethylethyl 4-(6-{5-[(ethylamino)carbonyl]-3-fluoro-2-methylphenyl}-1H-indazol-3-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate

HRID 2246626
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HRID 2246626 반응식
[CH2:1]([NH:3][C:4](=[O:23])[C:5]1[CH:10]=[C:9]([C:11]2[CH:19]=[C:18]3[C:14]([C:15](I)=[N:16][NH:17]3)=[CH:13][CH:12]=2)[C:8]([CH3:21])=[C:7]([F:22])[CH:6]=1)[CH3:2].CC1(C)C(C)(C)OB([C:32]2[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:36][CH:37]=2)O1.C(=O)([O-])O.[Na+]>C(O)(C)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([NH:3][C:4]([C:5]1[CH:6]=[C:7]([F:22])[C:8]([CH3:21])=[C:9]([C:11]2[CH:19]=[C:18]3[C:14]([C:15]([C:32]4[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH:33]=4)=[N:16][NH:17]3)=[CH:13][CH:12]=2)[CH:10]=1)=[O:23])[CH3:2]
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참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 178464894HCID 178464894, 화합물2회

생성물 1

HCID 588996041,1-dimethylethyl 4-(6-{5-[(ethylamino)carbonyl]-3-fluoro-2-methylphenyl}-1H-indazol-3-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate수율 66.5%

시약·촉매·용매 2

HCID 178418397
HCID 178418397, 화합물
촉매
HCID 3776Isopropanol용매

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온도
150 °C

실험 절차

A mixture of N-ethyl-3-fluoro-5-(3-iodo-1H-indazol-6-yl)-4-methylbenzamide (Intermediate 19, 2.34 g), 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (1.71 g), aqueous sodium hydrogen carbonate (1M, 11.1 ml) and tetrakis(triphenylphosphine)palladium(0) (129 mg) in isopropanol (10 ml) was divided into three portions then stirred in sealed vials at 150° C. for 25 min in a microwave oven. The reaction mixtures were combined, the solvent was removed under vacuum and the residue was partitioned between ethyl acetate and water. The organic layer was separated using a hydrophobic filter tube, the solvent was evaporated and the residue was purified by chromatography on a silica column eluting with an ethyl acetate:cyclohexane gradient, to give the title compound as a yellow foam (1.76 g).

후처리

  1. customThe reaction mixtures
  2. customthe solvent was removed under vacuum
  3. customthe residue was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. customthe solvent was evaporated
  6. customthe residue was purified by chromatography on a silica column
  7. washeluting with an ethyl acetate

출처 및 근거

ORD 기록
ord-38c79a5b6eac44198382e48a4a5dfdf0
출처 데이터셋
uspto-grants-2010_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07687532B2

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