Acetonitrile → HCID 178451060, compound

HRID 448613Notes

Reaction equation

HRID 448613 reaction equation
[NH2:1][C@H:2]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)[CH2:3][C@:4]([CH2:9][OH:10])([CH3:8])[C:5]([OH:7])=[O:6].CC#N.O1CCOCC1.[NH:33]1[CH:37]=[C:36]([C:38]([OH:40])=O)[N:35]=[N:34]1.CCN(C(C)C)C(C)C.CN(C(ON1N=N[C:60]2[CH:61]=[CH:62]C=N[C:59]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>Cl.CN(C=O)C.C(O)CCC>[CH2:59]([O:6][C:5](=[O:7])[C@@:4]([CH2:9][OH:10])([CH3:8])[CH2:3][C@H:2]([NH:1][C:38]([C:36]1[NH:35][N:34]=[N:33][CH:37]=1)=[O:40])[CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:16][CH:17]=1)[CH2:60][CH2:61][CH3:62]

Participants

10

Reactant 6

HCID 6342AcetonitrileHCID 312751,4-DioxaneHCID 81531Diisopropylethylamine2×HCID 1401204-Carboxy-1,2,3-triazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68181056(2S,4R)-4-Amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methylpentanoic acid

Product 1

HCID 178451060HCID 178451060, compoundYield 26.7%

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent2×

Procedure

(2S,4R)-4-Amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (76 mg, 242 μmol) in MeCN (0.4 mL, 8 mmol) and 4 M HCl in 1,4-dioxane (242 μL, 969 μmol) was combined with butan-1-ol (0.5 mL) at 60° C. The resulting mixture was stirred until solid precipitation was observed (˜30 minutes). The solvent was evaporated under vacuum and the solids were azeotroped in toluene and dried under vacuum. 1,2,3-Triazole-4-carboxylic acid (0.0274 g, 0.242 mmol), DIPEA (169 μL, 969 μmol) and HATU (92 mg, 242 μmol) were combined in DMF (0.2 mL) and stirred for 5 minutes at room temperature. This was then combined with the dried solids, predissolved in DMF (0.2 mL) and DIPEA (0.5 eq.). The resulting mixture was stirred for 15 minutes and the reaction was quenched with AcOH. The product was purified by preparative HPLC and lyophilized to yield the title compound (30 mg; purity 95%). MS m/z [M+H]+ calc'd for C26H32N4O4, 465.24. found 465.4.

Workup

  1. custom(˜30 minutes)
  2. customThe solvent was evaporated under vacuum
  3. customthe solids were azeotroped in toluene
  4. customdried under vacuum
  5. stirringstirred for 5 minutes at room temperature
  6. stirringThe resulting mixture was stirred for 15 minutes
  7. customthe reaction was quenched with AcOH
  8. customThe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-1df2a8ee6bb447838b53c117ec919e9d
Source dataset
uspto-grants-2013_07
Patent number
US08481044B2

Reaction notes

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