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Triethylamine → 5-[bis(Cyclopropylmethyl)amino]-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide

HRID 1874841
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HRID 1874841 반응식
[CH2:1]([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])[CH3:2].F[C:9](F)(F)[C:10](O)=O.NC1[CH:17]=[C:18]2[C:22](=[CH:23]C=1)[NH:21][C:20]([C:25]([NH:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([O:36][C:37]3[CH:42]=[C:41]([C:43]#[N:44])[CH:40]=[C:39]([Cl:45])[CH:38]=3)[C:30]=1[F:46])=[O:26])=[CH:19]2.[CH:47]1(C=O)C[CH2:48]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(OCC)(=O)C>[CH:2]1([CH2:1][N:3]([CH2:6][CH:7]2[CH2:10][CH2:9]2)[C:4]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:5]=2)[NH:21][C:20]([C:25]([NH:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([O:36][C:37]4[CH:42]=[C:41]([C:43]#[N:44])[CH:40]=[C:39]([Cl:45])[CH:38]=4)[C:30]=2[F:46])=[O:26])=[CH:19]3)[CH2:48][CH2:47]1
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참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 866448845-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate

생성물 1

HCID 684872255-[bis(Cyclopropylmethyl)amino]-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide
수율 37%

시약·촉매·용매 2

HCID 63651,1-Dichloroethane용매HCID 8857Ethyl Acetate용매

실험 절차

Triethylamine (0.049 mL, 0.355 mmol) was added to a suspension of 5-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate (0.207 g, 0.355 mmol) in dichloroethane (5 mL). To the resulting solution was added cyclopropanecarbaldehyde (0.027 mL, 0.355 mmol) and sodium triacetoxyborohydride (0.188 g, 0.887 mmol). After stirring at RT overnight, the reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by column chromatography (dichloromethane/methanol) to give the title compound (0.075 g, 37%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.23 (d, 1H), 8.89 (t, 1H), 7.80 (d, 1H), 7.43-7.55 (m, 3H), 7.33-7.41 (m, 1H), 7.24 (d, 1H), 6.86-7.00 (m, 3H), 4.54 (d, 2H), 3.16 (d, 4H), 0.75-1.05 (m, 2H), 0.21-0.57 (m, 4H), −0.05-0.26 (m, 4H). MS: m/z 577 (M+1).

후처리

  1. washwashed with saturated aqueous sodium bicarbonate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography (dichloromethane/methanol)

출처 및 근거

ORD 기록
ord-41c73b94fd72403e97071740de14e22f
출처 데이터셋
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08304419B2

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