1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-[1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazol-5-yl]propenoic acid methyl ester

HRID 1058421노트

반응식

HRID 1058421 반응식
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11](=[O:41])[CH:12](P(OC)(OC)=O)[NH:13][C:14](=[O:34])[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[Cl:33].[CH3:42][C:43]([CH3:59])([O:45][C:46]([N:48]1[C:52]2[CH:53]=[CH:54][C:55]([CH:57]=O)=[CH:56][C:51]=2[N:50]=[N:49]1)=[O:47])[CH3:44]>O1CCCC1>[CH3:9][O:10][C:11](=[O:41])/[C:12](/[NH:13][C:14](=[O:34])[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[Cl:33])=[CH:57]/[C:55]1[CH:54]=[CH:53][C:52]2[N:48]([C:46]([O:45][C:43]([CH3:42])([CH3:59])[CH3:44])=[O:47])[N:49]=[N:50][C:51]=2[CH:56]=1

참가 물질

5

반응물 3

HCID 664601,1,3,3-TetramethylguanidineHCID 11637374tert-Butyl 5-formyl-1H-benzo[d][1,2,3]triazole-1-carboxylateHCID 23560749Rac.-n-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

생성물 1

HCID 70027820(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-[1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazol-5-yl]propenoic acid methyl ester수율 88%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

1,1,3,3-Tetramethylguanidine (60 μL, 0.48 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 132; 109 mg, 0.22 mmol) in tetrahydrofuran (3 mL) at room temperature. 1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazole-5-carboxaldehyde (Example 40; 55 mg, 0.22 mmol) was added and the solution was stirred at room temperature for 42 h. After the solvents were removed under reduced pressure, the residue was partitioned between ethyl acetate (10 mL) and pH 6 phosphate buffer (5 mL). The organic phase was washed with pH 6 phosphate buffer, brine, 10% aqueous sodium bicarbonate solution and brine. Each of the aqueous layers was extracted in turn with ethyl acetate. The combined organic layers were dried (Na2SO4), filtered and evaporated to give crude (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-[1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazol-5-yl]propenoic acid methyl ester (120 mg) which was used directly in the next step.

후처리

  1. customAfter the solvents were removed under reduced pressure
  2. customthe residue was partitioned between ethyl acetate (10 mL) and pH 6 phosphate buffer (5 mL)
  3. washThe organic phase was washed with pH 6 phosphate buffer, brine, 10% aqueous sodium bicarbonate solution and brine
  4. extractionEach of the aqueous layers was extracted in turn with ethyl acetate
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated

출처 및 근거

ORD 기록
ord-fe192756bfc84784af3927818578d554
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06515124B2

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