Benzenamine, 4-(4-morpholinyl)- → HCID 22184652, compound

HRID 1181990Notes

Reaction equation

HRID 1181990 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([N:13]3[CH2:19][CH2:18][CH2:17][N:16]([CH3:20])[CH2:15][CH2:14]3)[CH:12]=1)[NH:9][C:8]([C:21]([OH:23])=O)=[CH:7][C:6]2=[O:24].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[O:66]1[CH2:71][CH2:70][N:69]([C:72]2[CH:78]=[CH:77][C:75]([NH2:76])=[CH:74][CH:73]=2)[CH2:68][CH2:67]1>CN(C)C=O.CO>[N:69]1([C:72]2[CH:73]=[CH:74][C:75]([NH:76][C:21]([C:8]3[NH:9][C:10]4[C:5]([C:6](=[O:24])[CH:7]=3)=[CH:4][C:3]([O:2][CH3:1])=[CH:12][C:11]=4[N:13]3[CH2:19][CH2:18][CH2:17][N:16]([CH3:20])[CH2:15][CH2:14]3)=[O:23])=[CH:77][CH:78]=2)[CH2:68][CH2:67][O:66][CH2:71][CH2:70]1

Participants

8

Reactant 5

HCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 22142171HCID 22142171, compound

Product 1

HCID 22184652HCID 22184652, compoundYield 69.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-1,4-dihydro-quinoline-2-carboxylic acid (2.10 mmol) (Reference Example 25b) and diisopropylethyl amine (1.4 mL, 8.6 mmol) in 34 mL dimethylformamide was added TBTU (1.40 g, 4.36 mmol) and HOBt (0.588 g, 4.35 mmol) followed by the addition of 4-morpholinoaniline (0.463 g, 2.60 mmol). The resulting dark brown solution was stirred at room temperature under nitrogen for 19 hours. The reaction was concentrated in vacuo and the resulting crude product was taken up in methylene chloride/methanol. Filtration of the resulting mixture afforded some product as a yellow solid. The filtrates were concentrated and partitioned between methylene chloride and saturated aqueous sodium bicarbonate. The organic layer was washed with saturated sodium bicarbonate, dried (MgSO4), and concentrated under vacuum to afford a brown solid. This was suspended in methanol and filtered to afford the desired product as a yellow solid (0.714 g, 69%). 1H NMR (300 MHz, DMSO, d6) δ 9.97 (bs, 1 H, NH), 7.67 (d, 2 H, Jo=8.8 Hz, ArH2′& H6′), 7.47 (bs, 1 H, ArH5), 7.00 (s, 1 H, C═CH), 6.99 (d, 2 H, Jo=8.8 Hz, ArH3′& H5′), 6.71 (bs, 1 H, ArH7), 3.85 (s, 3 H, OCH3), 3.75 (t, 4 H, J=4.6 Hz, OCH2CH2N), 3.70 (bs, 2 H, ArNCH2CH2CH2NCH3), 3.55 (bs, 2 H, ArNCH2CH2NCH3), 3.09 (t, 4 H, J=4.6 Hz, OCH2CH2N), 2.95 (bs, 2 H, ArNCH2CH2NCH3), 2.73 (bs, 2 H, ArNCH2CH2CH2NCH3), 2.36 (s, 3 H, NCH3), 2.07 (bs, 2 H ArNCH2CH2CH2NCH3); Mass Spec.: calc. for [C27H33N5O4+H]+ Theor. m/z=492; Obs. 492.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. filtrationFiltration of the resulting mixture
  3. customafforded some product as a yellow solid
  4. concentrationThe filtrates were concentrated
  5. custompartitioned between methylene chloride and saturated aqueous sodium bicarbonate
  6. washThe organic layer was washed with saturated sodium bicarbonate
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under vacuum
  9. customto afford a brown solid
  10. filtrationfiltered

Sources & evidence

ORD record
ord-2abca18483a84984af254b455878ff5d
Source dataset
uspto-grants-2007_10
Patent number
US07285662B2

Reaction notes

Loading…