Morpholine → HCID 56963636, compound

HRID 931450Notes

Reaction equation

HRID 931450 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]2[N:13]=[C:14]([C:18]3[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH2:25][C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)=[O:23])=[CH:20][CH:19]=3)[O:15][C:16]=2[CH3:17])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>CS(C)=O>[CH3:17][C:16]1[O:15][C:14]([C:18]2[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH2:25][C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)=[O:23])=[CH:20][CH:19]=2)=[N:13][C:12]=1[CH2:11][S:8]([C:5]1[CH:6]=[CH:7][C:2]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[CH:3][CH:4]=1)(=[O:10])=[O:9]

Participants

4

Reactant 2

HCID 8083MorpholineHCID 56963634HCID 56963634, compound

Product 1

HCID 56963636HCID 56963636, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of fluoride 48 (103 mg, 0.22 mmol) and morpholine (2 mL) in DMSO (1 mL) was stirred in a sealed tube at 130° C. for 16 h. The solvent was evaporated and the residue was suspended in ice/water (50 mL) for 1 h. The precipitate was filtered, washed with water (5 mL) and dried. The crude solid was purified by column chromatography, eluting with a gradient (0-10%) of MeOH/EtOAc, to give benzamide 50 (83 mg, 71%) as a white powder: mp (EtOAc) 208-210° C.; 1H NMR δ 9.23 (s, 1H, CONH), 8.57 (br s, 1H, H-2′), 8.47 (br d, J=4.5 Hz, 1H, H-6′), 8.00 (br d, J=8.5 Hz, 2H, H-2, H-6), 7.91 (br d, J=8.5 Hz, 2H, H-3, H-5), 7.74 (br d, J=7.8 Hz, 1H, H-4′), 7.54 (d, J=9.0 Hz, 2H, H-3″, H-5″), 7.37 (dd, J=7.8, 4.7 Hz, 1H, H-5′), 7.05 (d, J=9.0 Hz, 2H, H-2″, H-6″), 4.49-4.54 (m, 4H, CH2SO2, CH2N), 3.72 (br t, J=4.8 Hz, 4H, 2×CH2O), 3.27 (br t, J=4.8 Hz, 4H, 2×CH2N), 2.13 (s, 3H, CH3); 13C NMR δ 165.5, 157.8, 154.2, 149.7, 148.8, 148.0, 135.3, 135.1, 134.8, 129.7 (2), 128.8, 128.0 (2), 126.4, 126.0, 125.4 (2), 123.4, 113.3 (2), 65.6 (2), 53.2, 46.7 (2), 40.4, 9.6; MS m/z 533.7 (MH+, 100%). Anal. calcd for C28H28N4O5S: C, 63.14; H, 5.30; N, 10.52. Found: C, 62.94; H, 5.18; N, 10.51%.

Workup

  1. customThe solvent was evaporated
  2. waitthe residue was suspended in ice/water (50 mL) for 1 h
  3. filtrationThe precipitate was filtered
  4. washwashed with water (5 mL)
  5. customdried
  6. customThe crude solid was purified by column chromatography
  7. washeluting with a gradient (0-10%) of MeOH/EtOAc

Sources & evidence

ORD record
ord-204eb2205aac4aaa93bfa19953d530b1
Source dataset
uspto-grants-2016_03
Patent number
US09296732B2

Reaction notes

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