Toluene → (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]quinazolin-6-yl]-3-[(2S)-1-methylpyrrolidin-2-yl]prop-2-enamide

HRID 1397061노트

반응식

HRID 1397061 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([NH:27][C:28](=[O:38])[CH2:29]P(OCC)(OCC)=O)[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1(C)C=CC=CC=1.[CH3:56][N:57]1[CH2:61][CH2:60][CH2:59][C@H:58]1[CH:62]=O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([NH:27][C:28](=[O:38])/[CH:29]=[CH:62]/[C@@H:58]4[CH2:59][CH2:60][CH2:61][N:57]4[CH3:56])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

참가 물질

6

반응물 4

HCID 1140TolueneHCID 2733832Lithium HexamethyldisilazideHCID 53829761(2S)-1-methylpyrrolidine-2-carbaldehydeHCID 86667263N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]quinazolin-6-yl]-2-diethoxyphosphoryl-acetamide

생성물 1

HCID 67979668(E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]quinazolin-6-yl]-3-[(2S)-1-methylpyrrolidin-2-yl]prop-2-enamide수율 33%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

N-[4-[[3-Chloro-4-(2-pyridylmethoxy)phenyl]amino]quinazolin-6-yl]-2-diethoxyphosphoryl-acetamide 4f (277 mg, 0.50 mmol) was dissolved in 2.5 mL of tetrahydrofuran in a dry ice bath, followed by dropwise addition of a solution of lithium bis(trimethylsilyl)amide (1 M) in toluene (750 μL, 0.75 mmol). After stirring for 45 minutes, the reaction mixture was added with (2S)-1-methylpyrrolidine-2-carbaldehyde 1b (113 mg, 2 mmol), and stirred for 1 hour, then warmed up to room temperature and stirred for 12 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography with elution system A to obtain the title compound (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]quinazolin-6-yl]-3-[(2S)-1-methylpyrrolidin-2-yl]prop-2-enamide 4 (85 mg, yield 33.0%) as a yellow solid.

후처리

  1. stirringstirred for 1 hour
  2. stirringstirred for 12 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe resulting residue was purified by silica gel column chromatography with elution system

출처 및 근거

ORD 기록
ord-d71653fac9784a0294d2c5a263e10e01
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901140B2

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