Hydrochloric Acid → HCID 66857825, compound

HRID 2037682Notes

Reaction equation

HRID 2037682 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:29][CH2:30][C:31]([OH:33])=O)[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1C=CC2N(O)N=[N:40]C=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C.Cl>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:29][CH2:30][C:31]([NH2:40])=[O:33])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66857976HCID 66857976, compound

Product 1

HCID 66857825HCID 66857825, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-((R)-6-(4-fluorophenyl)-2-oxo-3-((S)-1-(4-(2,2,2-trifluoroethoxy)phenyl)ethyl)-1,3-oxazinan-6-yl)propanoic acid (145 mg, 1.37 mmol) in CH2Cl2 (5 mL) was added HOBt (167 mg, 1.24 mmol), EDCl (243 mg, 1.24 mmol) and DIEA (194 mg, 1.55 mmol) under NH3 at 0° C. The mixture was stirred at rt overnight. 1N HCl was added and the mixture was extracted with CH2Cl2. The organic layer was dried and concentrated to give the residue, which was purified by preparative HPLC to give 3-((R)-6-(4-fluorophenyl)-2-oxo-3-((S)-1-(4-(2,2,2-trifluoroethoxy)phenyl)ethyl)-1,3-oxazinan-6-yl)propanamide (21 mg, 15%). LC-MS Method 2 tR=1.16 min, m/z=491, 469, 425. 1H NMR (CDCl3, 400 MHz): 1.43 (d, 3H), 1.88-1.95 (m, 1H), 2.07-2.19 (m, 5H), 2.40 (m, 1H), 2.83 (m, 1H), 4.21 (m, 1H), 5.18 (s, 1H), 5.33 (s, 1H), 5.56 (m, 1H), 6.64 (d, 2H), 6.85 (d, 2H), 6.97 (t, 2H), 7.17 (m, 2H).

Workup

  1. extractionthe mixture was extracted with CH2Cl2
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customto give the residue, which
  5. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-151a7b013cf549088b6e91f190c18692
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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