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

HRID 1875018노트

반응식

HRID 1875018 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][N:69]([CH3:74])[CH2:70][C:71](O)=[O:72].C(N(C(C)C)CC)(C)C>CN(C=O)C.CCOC(C)=O.O>[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:71](=[O:72])[CH2:70][N:69]([CH3:74])[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

8

반응물 4

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 866448845-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetateHCID 131720136BOP chloride

생성물 1

HCID 59451476N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-[(N,N-dimethylglycyl)amino]-1H-indole-2-carboxamide수율 28%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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), N,N-dimethylglycine (0.011 g, 0.103 mmol) and diisopropylethylamine (0.090 mL, 0.514 mmol) in DMF (1 mL). The mixture was stirred at RT for 1 hr. The reaction mixture was diluted with EtOAc and water. The organic layer was washed with water, dried over sodium sulfate, filtered and concentrated. The residue was triturated with methanol and dried under vacuum to give the title compound (0.016 g, 28%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.51 (br. s., 1H), 9.52 (br. s., 1H), 8.96 (t, 1H), 7.94 (s, 1H), 7.78 (s, 1H), 7.41-7.54 (m, 2H), 7.36 (t, 1H), 7.30 (s, 2H), 7.07 (s, 1H), 4.53 (d, 2H), 2.22 (s, 6H). ES MS: m/z 553 (M).

후처리

  1. washThe organic layer was washed with water
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was triturated with methanol
  6. customdried under vacuum

출처 및 근거

ORD 기록
ord-5f28cdadb5ad43379a4102ca71a0e0d3
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304419B2

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