Acetyl chloride → N-acetyl-N-[4-[3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)-phenylamino]-3-cyano-7-(4-pyrrolidin-1-yl-piperidin-1-yl)quinolin-6-yl]acetamide

HRID 269778노트

반응식

HRID 269778 반응식
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][CH:15]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]1)[N:8]=[CH:7][C:6]([C:23]#[N:24])=[C:5]2[NH:25][C:26]1[CH:31]=[CH:30][C:29]([S:32][C:33]2[N:34]([CH3:38])[CH:35]=[CH:36][N:37]=2)=[C:28]([Cl:39])[CH:27]=1.C(N(CC)C1C=CC=CC=1)C.[C:51](Cl)(=[O:53])[CH3:52].CN1CC[CH2:58][C:57]1=[O:61]>>[C:51]([N:1]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:12]1[CH2:13][CH2:14][CH:15]([N:18]3[CH2:19][CH2:20][CH2:21][CH2:22]3)[CH2:16][CH2:17]1)[N:8]=[CH:7][C:6]([C:23]#[N:24])=[C:5]2[NH:25][C:26]1[CH:31]=[CH:30][C:29]([S:32][C:33]2[N:34]([CH3:38])[CH:35]=[CH:36][N:37]=2)=[C:28]([Cl:39])[CH:27]=1)[C:57](=[O:61])[CH3:58])(=[O:53])[CH3:52]

참가 물질

5

반응물 4

HCID 6367Acetyl chlorideHCID 7061N,N-DiethylanilineHCID 13387N-methyl-2-pyrrolidoneHCID 68460429HCID 68460429, 화합물

생성물 1

HCID 68461457N-acetyl-N-[4-[3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)-phenylamino]-3-cyano-7-(4-pyrrolidin-1-yl-piperidin-1-yl)quinolin-6-yl]acetamide

실험 절차

To a cold (0° C.-5° C.) solution of 1.2 g (2.14 mmol) of 6-amino-4-[3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)phenylamino]-7-(4-pyrrolidin-1-yl-piperidin-1-yl)quinoline-3-carbonitrile and 3.6 ml (22.6 mmol) of N,N-diethyl aniline in 18 mL of 1-methyl 2-pyrrolidinone is added dropwise 1.6 ml (21.2 mmol) of acetyl chloride. The resulting mixture is stirred at room temperature for 4 hours. The solvent is removed in vacuo to yield a residue, which is triturated with ether. A saturated solution of sodium bicarbonate is added to the resulting solid and the mixture is stirred, collected by filtration and dried in vacuo. Purification by silica gel chromatography (gradient 95:5methylene chloride/methanol to 4:1 methylene chloride/methanol) gives 738 mg of N-acetyl-N-[4-[3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)-phenylamino]-3-cyano-7-(4-pyrrolidin-1-yl-piperidin-1-yl)quinolin-6-yl]acetamide as a beige solid, mp 245-247° C.

후처리

  1. customThe solvent is removed in vacuo
  2. customto yield a residue, which
  3. customis triturated with ether
  4. additionA saturated solution of sodium bicarbonate is added to the resulting solid
  5. stirringthe mixture is stirred
  6. filtrationcollected by filtration
  7. customdried in vacuo
  8. customPurification by silica gel chromatography (gradient 95:5methylene chloride/methanol to 4:1 methylene chloride/methanol)

출처 및 근거

ORD 기록
ord-f0173913a77d4b719ce5404747cd293f
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07449460B2

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