4-Methylmorpholine → HCID 67995325, compound

HRID 2361378Notes

Reaction equation

HRID 2361378 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:11][NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[C:31]4[C:30]5[CH:29]=[CH:28][C:27]([O:32][CH2:33][CH2:34][O:35][CH3:36])=[CH:26][C:25]=5[NH:24][C:23]=4[C:22]([C:37]([O:39][CH3:40])=[O:38])=[N:21][N:20]=3)[C:14]=2[CH3:41])=[C:6]([CH:10]=1)[C:7](O)=[O:8].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[C:6]2[C:5]([CH2:11][N:12]([C:13]3[C:14]([CH3:41])=[C:15]([C:19]4[C:31]5[C:30]6[CH:29]=[CH:28][C:27]([O:32][CH2:33][CH2:34][O:35][CH3:36])=[CH:26][C:25]=6[NH:24][C:23]=5[C:22]([C:37]([O:39][CH3:40])=[O:38])=[N:21][N:20]=4)[CH:16]=[CH:17][CH:18]=3)[C:7]2=[O:8])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67995088HCID 67995088, compound

Product 1

HCID 67995325HCID 67995325, compoundYield 17.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-chloro-2-((3-(4-(methoxycarbonyl)-7-(2-methoxyethoxy)-5H-pyridazino [4,5-b]indol-1-yl)-2-methylphenylamino)methyl)benzoic acid (0.227 g, 0.394 mmol), BOP (0.366 g, 0.827 mmol), and N-methylmorpholine (0.273 mL, 2.482 mmol) in DMF (3.94 mL) under nitrogen was heated at 45° C. After 6 hr, the reaction was cooled to room temperature, dissolved in EtOAc (100 mL) and washed with water (3×25 mL) and brine (25 mL), dried over MgSO4, filtered and concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 24 g column eluting with 0-5% MeOH/CH2Cl2. Appropriate fractions were collected and concentrated in vacuo to give the desired product (0.0384 g, 0.069 mmol, 17.5% yield) as a light orange solid.

Workup

  1. washwashed with water (3×25 mL) and brine (25 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a residue which
  6. customwas purified by flash chromatography
  7. washeluting with 0-5% MeOH/CH2Cl2
  8. customAppropriate fractions were collected
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9736a2d5580046a3991b7719c567755d
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

Loading…