Triethylamine → (S)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoate

HRID 75832

반응식

HRID 75832 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:25])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:21]=[C:20]([C:22](O)=[O:23])[O:19][N:18]=2)=[CH:13][CH:12]=1.C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.Cl.[CH3:52][O:53][C:54](=[O:59])[C@H:55]([CH2:57][OH:58])[NH2:56].C(N(CC)CC)C>CN(C=O)C.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:25])[NH:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:21]=[C:20]([C:22]([NH:56][C@@H:55]([CH2:57][OH:58])[C:54]([O:53][CH3:52])=[O:59])=[O:23])[O:19][N:18]=2)=[CH:15][CH:16]=1

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2723730L-Serine, methyl ester, hydrochloride (1:1)HCID 673539813-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxylic acid

생성물 1

HCID 67352794(S)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoate수율 39%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8028Tetrahydrofuran용매

실험 절차

3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxylic acid (example 105, step 2, 1 g, 293 mmol) was dissolved in DMF (20 ml) and, to it N,N′-Dicyclohexyl carbodiimide (724 mg, 3.51 mmol) and 1-Hydroxy benzotriazole (593 mg, 4.39 mmol) were added. Reaction mixture was stirred RT for 10 minutes followed by the addition of L-serine methyl ester hydrochloride (683 mg, 4.39 mmol) dissolved in DMF (5 ml) neutralized with triethylamine (0.6 ml, 4.39 mmol). The above reaction mixture was stirred at RT for 8 hours. DMF was distilled off under reduced pressure to give pale brown solid, which was taken in THF. DCU precipitated out and was filtered off. Water was added and the aqueous layer was extracted with EtOAc. Organic layer was dried over Na2SO4 and concentrated under vacuum. Crude compound was purified through precipitation using DCM and petroleum ether to yield 500 mg (39%) of the required compound as white solid. MS: ES (−): m/z 441(M−1); ES (+): m/z 443 (M+1); 1HNMR (DMSO-d6; 300 MHz): δ 9.342 (s, 1H), 9.109 (d; 1H), 8.633 (s, 1H), 8.161 (t, 1H), 7.369 (d, 2H), 7.676 (s, 1H), 7.619 (d, 2H), 7.242 (m, 1H), 7.066 (t, 1H), 7.024 (m, 1H), 5.149 (t, 1H), 4.575 (m, 1H), 3.821 (t, 2H), 3.657 (s, 3H).

후처리

  1. additionwere added
  2. customReaction mixture
  3. customThe above reaction mixture
  4. stirringwas stirred at RT for 8 hours
  5. distillationDMF was distilled off under reduced pressure
  6. customto give pale brown solid, which
  7. customDCU precipitated out
  8. filtrationwas filtered off
  9. additionWater was added
  10. extractionthe aqueous layer was extracted with EtOAc
  11. dry with materialOrganic layer was dried over Na2SO4
  12. concentrationconcentrated under vacuum
  13. customCrude compound was purified through precipitation

출처 및 근거

ORD 기록
ord-34efe286c4624832b702390bc7862409
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835428B2

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