Oxygen → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)-amino]pentanoic Acid

HRID 1052913노트

반응식

HRID 1052913 반응식
[OH:1][N:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]=[N:3]1.CN(C(ON1N=N[C:20]2[CH:21]=[CH:22][C:23](=[CH:25][C:19]1=2)[Cl:24])=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O:46][C:47](=[O:61])[C@H:48]([OH:60])[CH2:49][C@H:50]([NH2:59])[CH2:51][C:52]1[CH:57]=[CH:56][C:55](Br)=[CH:54][CH:53]=1)C.ClC1C=C(B(O)O)C=CC=1.C([O-])([O-])=O.[K+].[K+].O=O>CN(C=O)C.O.CCO>[Cl:24][C:23]1[CH:25]=[C:19]([C:55]2[CH:54]=[CH:53][C:52]([CH2:51][C@@H:50]([NH:59][C:7]([C:5]3[N:4]=[N:3][N:2]([OH:1])[CH:6]=3)=[O:9])[CH2:49][C@@H:48]([OH:60])[C:47]([OH:61])=[O:46])=[CH:57][CH:56]=2)[CH:20]=[CH:21][CH:22]=1

참가 물질

11

반응물 7

HCID 977OxygenHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2734323(3-Chlorophenyl)boronic acidHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateHCID 534331041-Hydroxy-1H-1,2,3-triazole-4-carboxylic AcidHCID 67969401(2R,4R)-4-amino-5-(4-bromophenyl)-2-hydroxypentanoic acid ethyl ester

생성물 1

HCID 57377989(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)-amino]pentanoic Acid수율 20.5%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

1-Hydroxy-1H-1,2,3-triazole-4-carboxylic acid (17.6 mg, 136 μmol) and HCTU (56.4 mg, 136 μmol) were combined in DMF and stirred for 5 minutes at room temperature. DIPEA (71.2 μl, 409 μmol) and (2R,4R)-4-amino-5-(4-bromophenyl)-2-hydroxypentanoic acid ethyl ester (43 mg, 140 μmol) were added and the resulting mixture was stirred for 10 minutes. The reaction mixture was evaporated under reduced pressure and purified (C18 reverse phase column). The purified material was combined with 3-chlorophenylboronic acid, pinacol ester (48.1 mg, 202 μmol), K2CO3 (41.8 mg, 302 μmol), EtOH (1 ml) and water (0.3 ml). Oxygen was removed (high vacuum) and SilicaCat®Pd(0) (0.09 mmol/g loading; 112 mg, 10.1 μmol) was quickly added under nitrogen. The mixture was microwaved at 100° C. for 20 minutes, then concentrated. The material was redissolved in AcOH and purified by preparative HPLC to yield the title compound (12 mg; purity 95%). MS m/z [M+H]+ calc'd for C20H19ClN4O5, 431.10. found 431.4.

후처리

  1. stirringthe resulting mixture was stirred for 10 minutes
  2. customThe reaction mixture was evaporated under reduced pressure
  3. custompurified (C18 reverse phase column)
  4. additionwas quickly added under nitrogen
  5. customThe mixture was microwaved at 100° C. for 20 minutes
  6. concentrationconcentrated
  7. dissolutionThe material was redissolved in AcOH
  8. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-7dc7cf8831984f8f9ecf3943cc6c0aa2
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388145B2

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