4-Methylmorpholine → HCID 67358657, compound

HRID 2408838Notes

Reaction equation

HRID 2408838 reaction equation
Cl.Cl.[CH2:3]([N:10]1[CH2:18][CH2:17][C:13]2([CH2:16][NH:15][CH2:14]2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2([C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)[CH2:30][CH2:29][N:28]([CH2:31][C:32](O)=[O:33])[C:27]2=[O:35])=[CH:22][CH:21]=1.C(N=C=NCCCN(C)C)C.CN1CCOCC1>ClCCl>[CH2:3]([N:10]1[CH2:11][CH2:12][C:13]2([CH2:16][N:15]([C:32](=[O:33])[CH2:31][N:28]3[CH2:29][CH2:30][C:26]([C:23]4[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=4)([C:36]4[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=4)[C:27]3=[O:35])[CH2:14]2)[CH2:17][CH2:18]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 673571912-(3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acidHCID 67386428HCID 67386428, compound

Product 1

HCID 67358657HCID 67358657, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

7-Benzyl-2,7-diazaspiro[3.5]nonane dihydrochloride from Example 7F (0.237 g, 0.749 mmol), the product from Example 14D (0.248 g, 0.749 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.199 ml, 1.123 mmol) and N-methylmorpholine (0.247 ml, 2.247 mmol) were stirred together in dichloromethane (2 mL). After stirring overnight, the reaction mixture was diluted with dichloromethane (20 mL) and washed with 1 N HCl (10 mL), brine (10 mL), dried over magnesium sulfate and concentrated. The residue was loaded onto a GraceResolv 40 gm silica gel column and the product was eluted with a gradient of 0.4% methanol/dichloromethane containing 0.2 N NH3 to 6% methanol/dichloromethane containing 0.2 N NH3 to yield the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.39-7.15 (m, 9H), 6.99 (t, J=8.2, 4H), 3.97 (s, 2H), 3.72 (d, J=20.0, 4H), 3.53 (t, J=6.5, 2H), 3.46 (s, 2H), 2.75 (t, J=6.4, 2H), 2.32 (s, 4H), 1.73 (s, 4H); MS (ESI+) m/z 530.2 (M+H)+.

Workup

  1. washwashed with 1 N HCl (10 mL), brine (10 mL)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. washthe product was eluted with a gradient of 0.4% methanol/dichloromethane containing 0.2 N NH3 to 6% methanol/dichloromethane containing 0.2 N NH3

Sources & evidence

ORD record
ord-263ec0b8173e408080d06c23de5dc11f
Source dataset
uspto-grants-2014_08
Patent number
US08815869B2

Reaction notes

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