Triethylsilane → 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

HRID 1776406노트

반응식

HRID 1776406 반응식
FC(F)(F)S(O[C:7]1[C:8]([NH:34][C:35]2[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=2)=[N:9][C:10]([C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH2:22][C:23]3[C:28]([F:29])=[CH:27][C:26]([O:30][CH2:31][CH3:32])=[CH:25][C:24]=3[F:33])[N:14]=2)=[N:11][CH:12]=1)(=O)=O.C(P(C1C=CC=CC=1)C1C=CC=CC=1)CCP(C1C=CC=CC=1)C1C=CC=CC=1.C([SiH](CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:31]([O:30][C:26]1[CH:27]=[C:28]([F:29])[C:23]([CH2:22][N:15]2[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:13]([C:10]3[N:9]=[C:8]([NH:34][C:35]4[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=4)[CH:7]=[CH:12][N:11]=3)=[N:14]2)=[C:24]([F:33])[CH:25]=1)[CH3:32]

참가 물질

6

반응물 3

HCID 12052TriethylsilaneHCID 812191,3-Bis(diphenylphosphino)propaneHCID 86732435HCID 86732435, 화합물

생성물 1

HCID 867324342-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

100 mg of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl trifluoromethanesulfonate (1-7-2, 0.165 mmol, 1. eq.), 0.74 mg of palladium (II) acetate (0.003 mmol, 0.02 eq.) and 1.36 mg of propane-1,3-diylbis(diphenylphosphane) were dissolved in 1 ml of DMF under a nitrogen atmosphere. The mixture was heated to 60° C. bath temperature. Then 0.66 ml of triethylsilane (0.41 mmol, 2.5 eq.) were added. The resulting mixture was stirred at 60° C. bath temperature for 18 hours. Then the mixture was partitioned between saturated aq. sodium hydrogen carbonate solution and dichloromethane. The phases were separated and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were washed with brine, dried over a silicone filter and concentrated in vacuo. Preparative HPLC purification provided 16 mg (0.03 mmol, 20.1%) of the analytically pure target compound.

후처리

  1. customThen the mixture was partitioned between saturated aq. sodium hydrogen carbonate solution and dichloromethane
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted twice with dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over a silicone
  6. filtrationfilter
  7. concentrationconcentrated in vacuo
  8. customPreparative HPLC purification
  9. customprovided 16 mg (0.03 mmol, 20.1%) of the analytically pure target compound

출처 및 근거

ORD 기록
ord-5c2468c131ac45b483c3dca2d219c45d
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09265763B2

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