4-Methylmorpholine → HCID 178459118, compound

HRID 2365506Notes

Reaction equation

HRID 2365506 reaction equation
[CH:1]([O:4][CH2:5][CH2:6][CH2:7][NH:8][S:9]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15]([OH:17])=O)(=[O:11])=[O:10])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.Cl.Cl.[NH:54]1[C:58]2([CH2:63][CH2:62][NH:61][CH2:60][CH2:59]2)[CH2:57][NH:56]/[C:55]/1=[N:64]\[C:65]([C:67]1[C:72]([NH2:73])=[N:71][C:70]([NH2:74])=[C:69]([Cl:75])[N:68]=1)=[O:66]>CN(C=O)C.[OH-].[Na+]>[CH:1]([O:4][CH2:5][CH2:6][CH2:7][NH:8][S:9]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15]([N:61]1[CH2:62][CH2:63][C:58]2([NH:54]/[C:55](=[N:64]/[C:65]([C:67]3[C:72]([NH2:73])=[N:71][C:70]([NH2:74])=[C:69]([Cl:75])[N:68]=3)=[O:66])/[NH:56][CH2:57]2)[CH2:59][CH2:60]1)=[O:17])(=[O:10])=[O:11])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 670865933-(3-Isopropoxypropylsulfamoyl)benzoic acid2×HCID 178478673HCID 178478673, compound

Product 1

HCID 178459118HCID 178459118, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolvent2×

Procedure

To a solution of 3-(3-Isopropoxy-propylsulfamoyl)-benzoic acid (Intermediate V) (1.10 g, 3.65 mmol) in DMF (20 ml) is added HATU (1.53 g, 4.02 mmol) and N-methyl morpholine (1.204 ml, 10.95 mmol) and the solution is stirred at room temperature for 5 minutes. 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide dihydrochloride (Ex. 38) (1.60 g, 4.02 mmol) is added and the reaction stirred at room temperature for 45 minutes. The reaction mixture is diluted with 2N NaOH (150 ml) and the crude product extracted into EtOAc (2×250 ml). The organic phase is dried over MgSO4 and the solvent evaporated in vacuo to yield a yellow oil. Purification on a Waters preparative Delta 3000 HPLC using a gradient of water (+0.1% TFA) and acetonitrile yields a yellow oil. 2N NaOH is added to the oil and the product is extracted into EtOAc (2×400 ml). The organic phases are combined, dried over MgSO4 and the solvent concentrated in vacuo to a volume of approximately 150 ml. To this solution is added iso-hexane (400 ml) and a pale yellow solid precipitates. This solid is collected by filtration and rinsed with iso-hexane to afford the title compound; [M+H]+ 607.98; 1H Nmr (DMSO): 1.00 (6H, d, J=6.0 Hz), 1.55 (2H, m), 1.69-1.79 (4H, m), 2.81 (2H, t, 5.9 Hz), 3.29 (2H, tr, J=6.0 Hz), 3.42 (1H, m), 3.44 (2H, br), 3.29-3.82 (4H, m), 6.15-7.30 (3H, br), 7.66 (1H, d, J=7.4 Hz), 7.70 (1H, dd, J=7.4 Hz, J=7.4 Hz), 7.76 (1H, s), 7.86 (1H, d, J=7.4 Hz), 7.44-8.00 (1H, br), 8.00-9.05 (3H, br).

Workup

  1. stirringthe reaction stirred at room temperature for 45 minutes
  2. extractionthe crude product extracted into EtOAc (2×250 ml)
  3. dry with materialThe organic phase is dried over MgSO4
  4. customthe solvent evaporated in vacuo
  5. customto yield a yellow oil
  6. customPurification on a Waters preparative Delta 3000 HPLC
  7. customyields a yellow oil
  8. extractionthe product is extracted into EtOAc (2×400 ml)
  9. dry with materialdried over MgSO4
  10. concentrationthe solvent concentrated in vacuo to a volume of approximately 150 ml
  11. additionTo this solution is added iso-hexane (400 ml)
  12. customa pale yellow solid precipitates
  13. filtrationThis solid is collected by filtration
  14. washrinsed with iso-hexane

Sources & evidence

ORD record
ord-a56df81c51194457bffd1e9de11d2d61
Source dataset
uspto-grants-2014_04
Patent number
US08697687B2

Reaction notes

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