2-Amino-4-methylphenol → 2-{2-[3-(5-Cyano-pyrazin-2-yl)-ureido]-4-methyl-phenoxymethyl}-morpholine-4-carboxylic acid tert-butyl ester

HRID 418009

반응식

HRID 418009 반응식
[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[OH:9].[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][O:20][CH:19]([CH2:23][OH:24])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[CH3:25][C:26]1[CH:31]=[CH:30][C:29](O)=[C:28]([N+:33]([O-])=O)[CH:27]=1.ClC(Cl)(O[C:40](=[O:46])OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[NH2:57][C:58]1[N:59]=[CH:60][C:61]([C:64]#[N:65])=[N:62][CH:63]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C1(C)C=CC=CC=1>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][O:20][CH:19]([CH2:23][O:9][C:3]2[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[NH2:1])[CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12].[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][O:20][CH:19]([CH2:23][O:24][C:29]2[CH:30]=[CH:31][C:26]([CH3:25])=[CH:27][C:28]=2[NH:33][C:40]([NH:57][C:58]2[CH:63]=[N:62][C:61]([C:64]#[N:65])=[CH:60][N:59]=2)=[O:46])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

참가 물질

11

반응물 7

HCID 72642-Amino-4-methylphenolHCID 83914-Methyl-2-nitrophenolHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 2733832Lithium HexamethyldisilazideHCID 5201202tert-Butyl 2-(hydroxymethyl)morpholine-4-carboxylateHCID 139252945-Aminopyrazine-2-carbonitrile

생성물 2

HCID 666486682-{2-[3-(5-Cyano-pyrazin-2-yl)-ureido]-4-methyl-phenoxymethyl}-morpholine-4-carboxylic acid tert-butyl esterHCID 666489632-(2-Amino-4-methyl-phenoxymethyl)-morpholine-4-carboxylic acid tert-butyl ester

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

실험 절차

2-(2-Amino-4-methyl-phenoxymethyl)-morpholine-4-carboxylic acid tert-butyl ester (0.087 g, 0.270 mmol) was prepared from 2-amino-4-methyl-phenol according to methods of Compound 3, Steps 1 and 2 using 2-hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (prepared according to the procedure for Compound 2, Step 1 using the corresponding acid) and 4-methyl-2-nitro-phenol. It was combined with triphosgene (0.029 g, 0.10 mmol), toluene (2 mL) and Hunig's base (0.15 mL, 0.86 mmol), and stirred at room temperature for 25 min. The suspension then was transferred through a cannula to a cold solution (−78° C.) containing 5-amino-pyrazine-2-carbonitrile (0.032 g, 0.27 mmol), and lithium bis(trimethylsilyl)amide (0.27 mmol) in THF (1 mL), which had been stirring at −78° C. for 30 min. The reaction was allowed to warm, then was stirred for 16 h at room temperature. A precipitate formed and was collected by filtration to yield the desired product (0.043 g).

후처리

  1. customprepared
  2. customthen was transferred through a cannula to a cold solution (−78° C.)
  3. stirringhad been stirring at −78° C. for 30 min
  4. temperatureto warm
  5. stirringwas stirred for 16 h at room temperature
  6. customA precipitate formed
  7. filtrationwas collected by filtration

출처 및 근거

ORD 기록
ord-61a2bbade1e247088e592229fc70a6c3
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093244B2

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