4-Methylmorpholine → HCID 178508773, compound

HRID 2365514Notes

Reaction equation

HRID 2365514 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][N:6]1[C:11](=[O:12])[CH:10]=[CH:9][C:8]([C:13]([OH:15])=O)=[CH:7]1.Cl.Cl.[NH:22]1[C:26]2([CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH2:25][NH:24]/[C:23]/1=[N:32]\[C:33]([C:35]1[C:40]([NH2:41])=[N:39][C:38]([NH2:42])=[C:37]([Cl:43])[N:36]=1)=[O:34].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN1C(=O)CCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][N:6]1[C:11](=[O:12])[CH:10]=[CH:9][C:8]([C:13]([N:29]2[CH2:30][CH2:31][C:26]3([NH:22]/[C:23](=[N:32]/[C:33]([C:35]4[C:40]([NH2:41])=[N:39][C:38]([NH2:42])=[C:37]([Cl:43])[N:36]=4)=[O:34])/[NH:24][CH2:25]3)[CH2:27][CH2:28]2)=[O:15])=[CH:7]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27648571-(3,4-Difluorobenzyl)-6-oxo-1,6-dihydropyridine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178478673HCID 178478673, compound

Product 1

HCID 178508773HCID 178508773, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent3×

Procedure

A solution of 1-(3,4-Difluoro-benzyl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (0.15 mmol) in NMP (0.5 ml) is added to a solution of 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide dihydrochloride (Ex. 38) (0.049 g, 0.15 mmol) and N-methyl morpholine (0.033 ml, 0.30 mmol) in NMP (1 ml), followed by a solution of HATU (0.11 g, 0.3 mmol) in NMP (0.5 ml). The reaction mixture is shaken at room temperature overnight. The reaction mixture is purified by mass-directed preparative HPLC. Fractions containing pure product are eluted through SCX-2 cartridges (Biotage 1 g/6 ml cartridge), and the cartridge is washed with MeOH (4 ml), followed by 3M NH3 in MeOH solution (4 ml) to afford the title compound; [M+H]+ 572.0

Workup

  1. customThe reaction mixture is purified by mass-directed preparative HPLC
  2. additionFractions containing pure product
  3. washare eluted through SCX-2 cartridges (Biotage 1 g/6 ml cartridge)
  4. washthe cartridge is washed with MeOH (4 ml)

Sources & evidence

ORD record
ord-963691fd449b4fdd917e0d11b8e9e716
Source dataset
uspto-grants-2014_04
Patent number
US08697687B2

Reaction notes

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