Ammonia → HCID 58109378, compound

HRID 2037576Notes

Reaction equation

HRID 2037576 reaction equation
[F:1][CH:2]([F:31])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([N:12]2[CH2:17][CH2:16][C@:15]([CH2:25][CH2:26][C:27](O)=[O:28])([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[O:14][C:13]2=[O:30])[CH3:11])=[CH:6][CH:5]=1.C[N:33](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.N>CN(C=O)C.C1COCC1>[F:1][CH:2]([F:31])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([N:12]2[CH2:17][CH2:16][C@:15]([CH2:25][CH2:26][C:27]([NH2:33])=[O:28])([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[O:14][C:13]2=[O:30])[CH3:11])=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58109285HCID 58109285, compound

Product 1

HCID 58109378HCID 58109378, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-((R)-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)propanoic acid (0.0485 g, 0.11 mmol) in DMF (2 mL) was added HATU (0.2603 g, 0.68 mmol), DIPEA (0.5 mL), and 0.8 M NH3 in THF (3 mL). The mixture was stirred at rt for 22 h. After the solvents were removed in vacuo, the residue was purified by reversed-phase HPLC (SunFire™ Prep C18 OBD™ 5 μm 19×50 mm column, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 8 min and then 90% CH3CN/H2O, 0.1% CF3COOH over 2 min, flow rate 20 mL/min) to afford 0.0235 g (49%) of 3-((R)-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)propanamide. LC-MS Method 1 tR=1.48 min, m/z 459 (MNa+), 393; 1H NMR (400 MHz, CDCl3) δ 7.23-7.20 (m, 2H), 7.04-6.99 (m, 2H), 6.95 (d, J=8.2 Hz, 2H), 6.89 (d, J=8.5 Hz, 2H), 6.43 (t, J=73.8 Hz, 1H), 5.83-5.78 (m, 2H), 5.62 (q, J=7.0 Hz, 1H), 2.95-2.91 (m, 1H), 2.45 (m, 1H), 2.27-2.15 (m, 5H), 1.98 (m, 1H), 1.49 (d, J=7.0 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −81.51 (d, J=73.7 Hz), −114.66 (m).

Workup

  1. customAfter the solvents were removed in vacuo
  2. customthe residue was purified by reversed-phase HPLC (SunFire™ Prep C18 OBD™ 5 μm 19×50 mm column, 10%
  3. customover 8 min
  4. wait90% CH3CN/H2O, 0.1% CF3COOH over 2 min

Sources & evidence

ORD record
ord-34da292265de461299558d777abc8cc1
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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