Ammonia → HCID 58109449, compound

HRID 2037693Notes

Reaction equation

HRID 2037693 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:23][C:24](O)=[O:25])([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=1.C[N:29](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>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:23][C:24]([NH2:29])=[O:25])([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=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 59635805HCID 59635805, compound

Product 1

HCID 58109449HCID 58109449, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-((S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)acetic acid (0.0259 g, 0.059 mmol) in DMF (2 mL) was added HATU (0.2298 g, 0.60 mmol), DIPEA (0.5 mL), and 0.8 M NH3 in THF (4 mL). The mixture was stirred at rt for 2 d. 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 0.0146 g (57%) of 2-((S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)acetamide. LC-MS Method 1 tR=1.55 min, m/z 435, 437 (MH+), 391, 393; 1H NMR (400 MHz, CD3OD) δ 7.30-7.26 (m, 2H), 7.19-7.16 (m, 2H), 7.04-6.99 (m, 2H), 6.74 (d, J=8.5 Hz, 2H), 5.39 (q, J=7.0 Hz, 1H), 3.06-3.01 (m, 1H), 2.72-2.58 (m, 3H), 2.42-2.34 (m, 1H), 2.26-2.19 (m, 1H), 1.41 (d, J=7.0 Hz, 3H); 19F NMR (376 MHz, CD3OD) δ −116.70 (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-5737c22bd0894961905a826751e5b1db
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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