Acetonitrile → HCID 178459557, compound

HRID 535170Notes

Reaction equation

HRID 535170 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)[CH:44]([CH3:46])[CH3:45].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>Cl.CN(C=O)C.CC(O)C>[CH:44]([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)([CH3:46])[CH3:45]

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 178459557HCID 178459557, compoundYield 34.9%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 3776IsopropanolSolventHCID 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 propan-2-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 (38 mg; purity 95%). MS m/z [M+H]+ calc'd for C25H30N4O4, 451.23. found 451.4.

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-ff7af706c7644914b8297369248e5254
Source dataset
uspto-grants-2014_10
Patent number
US08853427B2

Reaction notes

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