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Hydrochloric Acid → (S)-2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoic acid

HRID 75833
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HRID 75833 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:32])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:21]=[C:20]([C:22]([NH:24][C@@H:25]([CH2:30][OH:31])[C:26]([O:28]C)=[O:27])=[O:23])[O:19][N:18]=2)=[CH:13][CH:12]=1.CC(C)C(NC(C1ON=C(C2C=CC(NC(NC3C=CC(C(F)(F)F)=CC=3)=O)=CC=2)C=1)=O)C(OC)=O.O.[OH-].[Li+].Cl>C1COCC1.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:32])[NH:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:21]=[C:20]([C:22]([NH:24][C@@H:25]([CH2:30][OH:31])[C:26]([OH:28])=[O:27])=[O:23])[O:19][N:18]=2)=[CH:15][CH:16]=1
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참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 67352407Methyl 3-methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoateHCID 67352794(S)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoate

생성물 1

HCID 67353556
(S)-2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoic acid
수율 44%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

(S)-methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoate (compound of Example 275, 200 mg, 0.452 mmol) was dissolved in THF and water in 2:1 ratio. Lithium hydroxide monohydrate (29 mg, 0.678 mmol) was added and the reaction mixture was stirred at RT for 4 hours. The reaction mixture was acidified with dilute HCl and extracted with EtOAc. Organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure. Crude compound was purified by washing with methanol to get 85 mg (44%) of the title compound. MS: ES (−): m/z 427 (M−1); ES (+): m/z 429(M+1); 1HNMR (DMSO-d6, 300 MHz): δ 9.377 (s, 1H), 8.885 (d, 1H), 8.701 (s, 1H), 8.178 (t, 1H), 7.892 (d, 2H), 7.692 (s, 1H), 7.641 (d, 2H), 7.289 (m, 1H), 7.188 (t, 1H), 7.066 (m, 1H), 4.492 (m, 1H), 3.868 (m, 2H), 3.554 (m, 1H), 3.087 (s, 3H).

후처리

  1. extractionextracted with EtOAc
  2. customOrganic layer was separated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customCrude compound was purified
  6. washby washing with methanol

출처 및 근거

ORD 기록
ord-e072460a403343d08f487d11b723860d
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08835428B2

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