Diisopropylethylamine → N1-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

HRID 2237159노트

반응식

HRID 2237159 반응식
ClC1C=C(OC2C=CC=CC2(N)F)N=CN=1.[Cl:17][C:18]1[N:23]=[CH:22][N:21]=[C:20]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31]C(NC(=O)CC3C=CC(F)=CC=3)=S)=[CH:27][C:26]=2[F:45])[CH:19]=1.[F:46][C:47]1[CH:52]=[CH:51][C:50]([NH:53][C:54](=[O:59])[CH2:55][C:56]([OH:58])=O)=[CH:49][CH:48]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[Cl:17][C:18]1[N:23]=[CH:22][N:21]=[C:20]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:56](=[O:58])[CH2:55][C:54]([NH:53][C:50]3[CH:49]=[CH:48][C:47]([F:46])=[CH:52][CH:51]=3)=[O:59])=[CH:27][C:26]=2[F:45])[CH:19]=1

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 43418433-(4-Fluorophenylamino)-3-oxopropanoic acid2회HCID 115538441-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thioureaHCID 866014734-Chloro-6-(2-amino-2-fluorophenoxy)pyrimidine

생성물 1

HCID 59852939N1-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide수율 78%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of 4-chloro-6-(2-amino-2-fluorophenoxy)pyrimidine (29 mg, 0.12 mmol, Compound B of Example 2), 3-(4-fluorophenylamino)-3-oxopropanoic acid (26 mg, 0.13 mmol, Compound B of Example 1) in DMF (1.5 mL) was treated with DIPEA (24 μl, 0.14 mmol) and TBTU (46 mg, 0.14 mmol). The reaction mixture was stirred at RT overnight, diluted with EtOAc (25 mL), and the organic phase was washed with brine (3×20 mL), dried (MgSO4) and concentrated. The product was purified by flash chromatography using 1-3% MeOH in CH2Cl2 as the eluent to give the title compound as a white solid (35 mg, 78%). 1H NMR (DMSO-d6) δ 10.49 (s, 1H), 10.25 (s, 1H), 8.65 (s, 1H), 7.78 (d, 1H, J=12.1 Hz), 7.63-7.57 (m, 3H), 7.40-7.34 (m, 2H), 7.16 (t, 2H, J=8.8 Hz), 3.48 (s, 2H); MS(ESI+) m/z 419.21 (M+H)+.

후처리

  1. washthe organic phase was washed with brine (3×20 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe product was purified by flash chromatography

출처 및 근거

ORD 기록
ord-d67e0df3acd846859469440f1a8191f3
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07714138B2

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