4-Methylmorpholine → HCID 178450772, compound

HRID 386697Notes

Reaction equation

HRID 386697 reaction equation
[C:1]([O:5][C:6]([C:8]1([CH2:12][NH:13][S:14]([C:17]2[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=2)[C:20](O)=[O:21])(=[O:16])=[O:15])[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:57]1[C:61]2([CH2:66][CH2:65][NH:64][CH2:63][CH2:62]2)[CH2:60][NH:59]/[C:58]/1=[N:67]\[C:68]([C:70]1[C:75]([NH2:76])=[N:74][C:73]([NH2:77])=[C:72]([Cl:78])[N:71]=1)=[O:69]>CN(C=O)C>[C:1]([O:5][C:6]([C:8]1([CH2:12][NH:13][S:14]([C:17]2[CH:25]=[CH:24][CH:23]=[C:19]([C:20]([N:64]3[CH2:65][CH2:66][C:61]4([NH:57]/[C:58](=[N:67]/[C:68]([C:70]5[C:75]([NH2:76])=[N:74][C:73]([NH2:77])=[C:72]([Cl:78])[N:71]=5)=[O:69])/[NH:59][CH2:60]4)[CH2:62][CH2:63]3)=[O:21])[CH:18]=2)(=[O:15])=[O:16])[CH2:9][CH2:10][CH2:11]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

6

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 667975323-[(1-tert-Butoxycarbonyl-cyclobutylmethyl)-sulfamoyl]-benzoic acidHCID 178508760HCID 178508760, compound

Product 1

HCID 178450772HCID 178450772, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-[(1-tert-butoxycarbonyl-cyclobutylmethyl)-sulfamoyl]-benzoic acid (Int. AC) (1.37 g, 3.71 mmol) in DMF (20 ml) was treated with N-methylmorpholine (1.631 ml, 14.83 mmol) and HATU (1.41 g, 3.71 mmol) followed by 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide (1.27 g, 3.89 mmol). The reaction mixture was stirred at RT for 2 h and then partitioned between EtOAc and water. The organic portion was separated and washed with 0.5M aqueous 1,5,7-triazabicyclo[4.4.0]dec-5-ene solution, brine, dried over MgSO4 and concentrated in vacuo. Purification of the resulting oil by chromatography on silica eluting with 5-8% MeOH in iso-hexane afforded the title compound; LC-MS Rt 1.03 mins; 676.4 [M+H]+, Method 2minLC_v003.

Workup

  1. custompartitioned between EtOAc and water
  2. customThe organic portion was separated
  3. washwashed with 0.5M aqueous 1,5,7-triazabicyclo[4.4.0]dec-5-ene solution, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the resulting oil by chromatography on silica eluting with 5-8% MeOH in iso-hexane

Sources & evidence

ORD record
ord-ba608c22e74b4c8c82369acfb54e11a0
Source dataset
uspto-grants-2013_02
Patent number
US08372845B2

Reaction notes

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