Triethylamine → HCID 118659432, compound

HRID 1477242Notes

Reaction equation

HRID 1477242 reaction equation
C(O)(=O)C(O)=O.[CH3:7][O:8][C:9](=[O:23])[C@@H:10]([NH2:22])[C:11]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])([CH3:13])[CH3:12].[OH:24][CH2:25][C@@H:26]1[CH2:28][C@H:27]1[C:29]#[C:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[CH:37]=[C:36]([C:41](O)=[O:42])[CH:35]=[CH:34]2.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C>[C:18]([O:17][C:15]([NH:14][C:11]([CH3:13])([CH3:12])[C@H:10]([NH:22][C:41]([C:36]1[CH:35]=[CH:34][C:33]2[C:38](=[CH:39][CH:40]=[C:31]([C:30]#[C:29][C@@H:27]3[CH2:28][C@H:26]3[CH2:25][OH:24])[CH:32]=2)[CH:37]=1)=[O:42])[C:9]([O:8][CH3:7])=[O:23])=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117630543HCID 117630543, compoundHCID 118659535HCID 118659535, compound

Product 1

HCID 118659432HCID 118659432, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirring suspension of (S)-methyl-2-amino-3-((tert-butoxycarbonyl)amino)-3-methylbutanoate oxalate (6.3, 1.6 g, 4.9 mmol) and 6-(((trans)-2-(hydroxymethyl)cyclopropyl)ethynyl)-2-naphthoic acid (6.2, 1.0 g, 3.8 mmol) in ACN (10 mL) at 0° C. was added triethylamine (2.1 mL, 15 mmol), followed by the portionwise addition of a solution of HATU (3.0 g, 7.9 mmol) in ACN (10 mL) and the reaction mixture was stirred at 0° C. for 75 min. The reaction was concentrated under reduced pressure to yield a residue, which was partitioned between MTBE and water. The organic layer was washed with 1M citric acid, water, saturated sodium bicarbonate (2×), saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give (S)-methyl 3-((tert-butoxycarbonyl)amino)-2-(6-(((trans)-2-(hydroxymethyl)cyclopropyl)ethynyl)-2-naphthamido)-3-methylbutanoate (6.4), which was carried through to the next step without further purification.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customto yield a residue, which
  3. customwas partitioned between MTBE and water
  4. washThe organic layer was washed with 1M citric acid, water, saturated sodium bicarbonate (2×), saturated sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cb5e3c6ebde14b749ef30879a4316a69
Source dataset
uspto-grants-2016_08
Patent number
US09403758B2

Reaction notes

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