Triethylamine → HCID 59608133, compound

HRID 1469687Notes

Reaction equation

HRID 1469687 reaction equation
[CH3:1][O:2][C:3]1[O:4][C:5]([C:8]([OH:10])=O)=[CH:6][N:7]=1.Cl.[NH2:12][C@H:13]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:25][CH:24]=1)[CH2:14][C@@H:15]([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.C(Cl)Cl>[C:26]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:25]=[CH:24][C:23]([CH2:22][C@@H:13]([NH:12][C:8]([C:5]2[O:4][C:3]([O:2][CH3:1])=[N:7][CH:6]=2)=[O:10])[CH2:14][C@@H:15]([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:28][CH:27]=1

Participants

7

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 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochlorideHCID 553038672-Methoxyoxazole-5-carboxylic acid

Product 1

HCID 59608133HCID 59608133, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-methoxyoxazole-5-carboxylic acid, intermediate 22, (68 mg, 0.47 mmol) in DMF (2 mL) and DCM (2 mL) is added (2R,4S)-ethyl 4-amino-5-(biphenyl-4-yl)-2-methylpentanoate hydrochloride (150 mg, 0.43 mmol), HATU (246 mg, 0.65 mmol), and triethylamine (180 μL, 1.29 mmol). After stirring the reaction for 2 hours at room temperature, the reaction is quenched with H2O, and the crude is diluted in EtOAc. The organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O(0.1% TFA)/CH3CN), and then lyophilized to give (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxyoxazole-5-carboxamido)-2-methylpentanoate (175 mg). HPLC retention time=1.71 minutes (condition A); MS 437.5 (M+1); 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.20 (d, J=7.1 Hz, 3 H) 1.25 (t, J=7.1 Hz, 3 H) 1.65 (ddd, J=14.3, 10.0, 4.3 Hz, 1 H) 1.96-2.10 (m, 1 H) 2.63 (ddd, J=9.4, 7.1, 4.2 Hz, 1 H) 2.92 (dd, J=13.9, 6.3 Hz, 1 H) 2.99 (dd, J=13.9, 6.3 Hz, 1 H) 4.11 (s, 3 H) 4.12-4.18 (m, 2 H) 4.34-4.54 (m, 1 H) 6.15 (d, J=8.8 Hz, 1 H) 7.28 (d, J=8.3 Hz, 2 H) 7.31-7.37 (m, 1 H) 7.40-7.47 (m, 3 H) 7.54 (d, J=8.3 Hz, 2 H) 7.59 (dd, J=8.3, 1.26 Hz, 2 H)

Workup

  1. customthe reaction for 2 hours at room temperature
  2. customthe reaction is quenched with H2O
  3. additionthe crude is diluted in EtOAc
  4. washThe organic layer is washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O(0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-226e28057a5a49bd90a856fed0ae538d
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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