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

HRID 1052913Notes

Reaction equation

HRID 1052913 reaction equation
[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

Participants

11

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-7dc7cf8831984f8f9ecf3943cc6c0aa2
Source dataset
uspto-grants-2016_07
Patent number
US09388145B2

Reaction notes

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