1-(4-(6-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea → 1-[4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl]-3-[(4-fluorophenyl)acetyl]thiourea

HRID 1670233노트

반응식

HRID 1670233 반응식
N[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19](=[O:28])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[S:17])=[CH:11][C:10]=2[F:29])[CH:3]=1.F[C:31]1C=CC(CC(N=C=S)=O)=CC=1>C(Cl)Cl>[NH2:5][C:6]1[CH:31]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19](=[O:28])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[S:17])=[CH:11][C:10]=2[F:29])[CH:3]=[CH:2][N:7]=1

참가 물질

4

반응물 2

HCID 115389121-(4-(6-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea2회HCID 231532482-(4-Fluorophenyl)acetyl isothiocyanate

생성물 1

HCID 231530171-[4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl]-3-[(4-fluorophenyl)acetyl]thiourea수율 38.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

4-Fluorophenylacetylchloride (Aldrich, 0.017 mL, 0.126 mmol, 2.5 eq) was added to a solution of sodium thiocyanate (0.014 g, 0.176 mmol, 3.5 eq) in ethyl acetate (1.0 mL) at room temperature and the reaction mixture was stirred for 1.5 h to afford a 2-(4-fluorophenyl)ethanoyl isothiocyanate solution (0.126 M). 4-(4-Amino-2-fluorophenoxy)pyridin-2-amine (Compound B of Example 24, 0.011 g, 0.050 mmol, 1.0 eq) was dissolved in CH2Cl2 (1.0 mL) and 2-(4-fluorophenyl)ethanoyl isothiocyanate (0.126 M, 0.50 mL, 0.063 mmol, 1.3 eq) was added and the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was concentrated in vacuo and the resulting residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 0-6% MeOH in CHCl3) to afford the title compound (0.008 g, 38%) as a solid. 1H NMR (CD3OD) δ 7.85-7.95 (m, 1H), 7.67-7.69 (m, 1H), 7.13-7.28 (m, 4H), 6.95-7.00 (m, 2H), 6.05-6.15 (m, 1H), 5.90-5.91 (m, 1H), 3.65 (s, 2H); MS (ESI+) m/z 415 (M+H)+; HRMS (ESI+) calculated: 415.1040. found: 415.1041.

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe resulting residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 0-6% MeOH in CHCl3)

출처 및 근거

ORD 기록
ord-1e6863441a1c4127b3318bbea5895db4
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989477B2

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