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Ethyl Acetate → N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenylamino)isonicotinamide

HRID 2374020
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인쇄 미리보기

반응식

HRID 2374020 반응식
C(OC1C=[CH:13][C:12]([NH:15][C:16]2[N:21]=CN=[C:18]([O:22][C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:42])[CH2:31][C:32](NC4C=CC(F)=CC=4)=O)=[CH:25][C:24]=3[F:43])[CH:17]=2)=CC=1)C1C=CC=CC=1.CCO[C:47]([CH3:49])=O.C([O-])(O)=O.[Na+]>ClCCCl>[NH2:21][C:16]1[CH:17]=[C:18]([O:22][C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:42])[C:31]3[CH:32]=[CH:12][N:15]=[C:16]([NH:21][C:47]4[CH:49]=[CH:25][C:24]([F:43])=[CH:23][CH:28]=4)[CH:17]=3)=[CH:25][C:24]=2[F:43])[CH:13]=[CH:12][N:15]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 59853038N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide2회

생성물 1

HCID 46851683N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenylamino)isonicotinamide수율 6.3%

시약·촉매·용매 1

HCID 11
1,2-Dichloroethane
용매
2회

실험 절차

A solution of 4-(4-amino-2-fluorophenoxy)pyridine-2-amine (Compound B of Example 24, 450 mg, 2.1 mmol) in 1,2-dichloroethane (10 mL) was added slowly to a solution of acylchloride obtained above in 1,2-dichloroethane (10 mL) at ice bath temperature with stirring. The reaction mixture was allowed to stand at rt overnight. To the reaction mixture were added EtOAc (150 mL) and saturated aq. NaHCO3 solution (50 mL). The EtOAc layer was separated, dried over MgSO4 and concentrated in vacuo. The residue was purified by preparative HPLC to obtain the title compound (69 mg, 6.3%) as a yellow solid (bis-TFA salt). 1H NMR (DMSO-d6) δ 10.90 (s, 1H), 9.32 (s, 1H), 8.27 (d, 1H, J=5.5 Hz), 7.92-7.07 (m, 11H), 6.68 (dd, 1H, J=7.1, 2.2 Hz), 6.10 (d, 1H, J=2.2 Hz); MS(ESI+) m/z 217.9 (M+H)+.

후처리

  1. customThe EtOAc layer was separated
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-d22e3af67bbf4cd7b7383754c7106805
출처 데이터셋
uspto-grants-2008_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07459562B2

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