1-Hydroxybenzotriazole → Rac.-n-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

HRID 1058408노트

반응식

HRID 1058408 반응식
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[Cl:25][C:26]1[CH:34]=[C:33]([C:35]([NH:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([OH:45])[CH:40]=2)=[O:36])[CH:32]=[C:31]([CH3:46])[C:27]=1[C:28]([OH:30])=O.[CH3:47][O:48][C:49](=[O:58])[CH:50]([P:52]([O:56][CH3:57])([O:54][CH3:55])=[O:53])[NH2:51].COC(=O)C(P(OC)(OC)=O)NC(OCC1C=CC=CC=1)=O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CO.C(OCC)(=O)C>[CH3:47][O:48][C:49](=[O:58])[CH:50]([P:52]([O:54][CH3:55])([O:56][CH3:57])=[O:53])[NH:51][C:28](=[O:30])[C:27]1[C:31]([CH3:46])=[CH:32][C:33]([C:35]([NH:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([OH:45])[CH:40]=2)=[O:36])=[CH:34][C:26]=1[Cl:25]

참가 물질

8

반응물 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2734718Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetateHCID 11084793Methyl 2-amino-2-(dimethoxyphosphoryl)acetateHCID 186730542-Chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoic acid

생성물 1

HCID 23560749Rac.-n-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester수율 15%

시약·촉매·용매 1

HCID 21584119Ethylacetate methanol용매

실험 절차

O-(Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (645 mg, 1.7 mmol) was added to a solution of 2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoic acid (Example 112; 520 mg, 1.6 mmol) and rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-(benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (370 mg, 1.9 mmol). 1-hydroxybenzotriazole (255 mg, 1.9 mmol) was then added, followed by diisopropylethylamine (1.25 mL, 7.2 mmol). The solution was stirred at room temperature for 65 h and then it was evaporated to dryness under high vacuum to remove N,N-dimethylformamide. The residue was partitioned between ethyl acetate (50 mL) and saturated sodium bicarbonate solution (25 mL). The ethyl acetate layer was washed with brine, 0.5N hydrochloric acid solution and brine. Each of the aqueous layers was extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4), filtered, evaporated and the residue was chromatographed over silica gel (50-100% ethyl acetate/hexanes, then 5-25% methanol/ethyl acetate) to give rac.-N-[2-chloro4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (120 mg, 15% yield).

후처리

  1. customit was evaporated to dryness under high vacuum
  2. customto remove N,N-dimethylformamide
  3. customThe residue was partitioned between ethyl acetate (50 mL) and saturated sodium bicarbonate solution (25 mL)
  4. washThe ethyl acetate layer was washed with brine, 0.5N hydrochloric acid solution and brine
  5. extractionEach of the aqueous layers was extracted with ethyl acetate
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customthe residue was chromatographed over silica gel (50-100% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-fa1d13c65d0b42c081bbc6ba3f8fd459
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06515124B2

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