Diisopropylethylamine → N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-({3-[(1,1-dimethylethyl)oxy]propanoyl}amino)-1H-indole-2-carboxamide

HRID 1875020노트

반응식

HRID 1875020 반응식
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl-].FC(F)(F)C(O)=O.[NH2:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[NH:42][C:41]([C:46]([NH:48][CH2:49][C:50]1[CH:55]=[CH:54][C:53]([Cl:56])=[C:52]([O:57][C:58]3[CH:63]=[C:62]([C:64]#[N:65])[CH:61]=[C:60]([Cl:66])[CH:59]=3)[C:51]=1[F:67])=[O:47])=[CH:40]2.[CH3:68][C:69]([O:72][CH2:73][CH2:74][C:75](O)=[O:76])([CH3:71])[CH3:70].C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:56][C:53]1[CH:54]=[CH:55][C:50]([CH2:49][NH:48][C:46]([C:41]2[NH:42][C:43]3[C:39]([CH:40]=2)=[CH:38][C:37]([NH:36][C:75](=[O:76])[CH2:74][CH2:73][O:72][C:69]([CH3:71])([CH3:70])[CH3:68])=[CH:45][CH:44]=3)=[O:47])=[C:51]([F:67])[C:52]=1[O:57][C:58]1[CH:63]=[C:62]([C:64]#[N:65])[CH:61]=[C:60]([Cl:66])[CH:59]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 27609493-(tert-Butoxy)propionic acidHCID 866448845-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetateHCID 131720136BOP chloride

생성물 1

HCID 59451555N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-({3-[(1,1-dimethylethyl)oxy]propanoyl}amino)-1H-indole-2-carboxamide수율 58.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

BOP chloride (0.079 g, 0.309 mmol) was added to a solution of 5-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate (0.060 g, 0.103 mmol), 3-[(1,1-dimethylethyl)oxy]propanoic acid (0.015 mL, 0.103 mmol) and diisopropylethylamine (0.090 mL, 0.514 mmol) in DMF (1 mL). the mixture was stirred at room temperature for 1 hr. The reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (hexane:ethyl acetate) to give the title compound (0.036 g, 58%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.49 (s, 1H), 9.69 (s, 1H), 8.95 (t, 1H), 7.95 (s, 1H), 7.77 (d, 1H), 7.40-7.52 (m, 3H), 7.36 (t, 1H), 7.26-7.32 (m, 1H), 7.21 (d, 1H), 7.06 (s, 1H), 4.52 (d, 2H), 3.57 (t, 2H), 2.41 (t, 2H), 1.09 (s, 9H). ES MS: m/z 597 (M+1).

후처리

  1. extractionThe reaction mixture was extracted with ethyl acetate and water
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (hexane:ethyl acetate)

출처 및 근거

ORD 기록
ord-6945d6d5fbec4c1383596a4825f2cf07
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304419B2

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