Methanesulfonamide → HCID 58109469, compound

HRID 2037577Notes

Reaction equation

HRID 2037577 reaction equation
[F:1][CH:2]([F:30])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([N:12]2[CH2:17][CH2:16][C@@:15]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)([CH2:18][CH2:19][CH2:20]O)[O:14][C:13]2=[O:29])[CH3:11])=[CH:6][CH:5]=1.[CH3:31][S:32]([NH2:35])(=[O:34])=[O:33]>C1(C)C=CC=CC=1>[F:1][CH:2]([F:30])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([N:12]2[CH2:17][CH2:16][C@:15]([CH2:18][CH2:19][CH2:20][NH:35][S:32]([CH3:31])(=[O:34])=[O:33])([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[O:14][C:13]2=[O:29])[CH3:11])=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 72879MethanesulfonamideHCID 58109301HCID 58109301, compound

Product 1

HCID 58109469HCID 58109469, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of (R)-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (0.0332 g, 0.0784 mmol) and methanesulfonamide (0.0549 g, 0.577 mmol) in dry toluene (2 mL) was added (cyanomethene)tributylphosphorane (CMBP, 0.1720 g, 0.713 mmol) at rt under N2. The mixture was stirred for 19 h at rt. 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 0.0137 g (35%) of N-(3-((R)-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)propyl)methanesulfonamide. LC-MS Method 1 tR=1.64 min, m/z=523 (MNa+), 501 (MH+), 171; 1H NMR (400 MHz, CD3OD) δ 7.24-7.21 (m, 2H), 7.01 (t, J=8.6 Hz, 2H), 6.92 (d, J=8.8 Hz, 2H), 6.83 (d, J=8.5 Hz, 2H), 6.65 (t, J=73.8 Hz, 1H), 5.45 (q, J=7.0 Hz, 1H), 3.04-3.00 (m, 1H), 2.93-2.86 (m, 2H), 2.77 (s, 3H), 2.38-2.34 (m, 1H), 2.22-2.09 (m, 2H), 1.92-1.82 (m, 2H), 1.58-1.50 (m, 1H), 1.44 (d, J=7.0 Hz, 3H), 1.26-1.18 (m, 1H); 19F NMR (376 MHz, CD3OD) δ −83.93 (d, J=75.0 Hz), −117.33 (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-24aeeec70f5f48f6a664d5c1451168fd
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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