4-Methylmorpholine → HCID 11248247, compound

HRID 915342Notes

Reaction equation

HRID 915342 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH:15]=[CH:14][CH:13]=[CH:12]3)=[CH:8][CH:9]=2)[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:3]1[C:22](O)=[O:23].Cl.CN(C)CCCN=C=NCC.Cl.C([O:40][C:41](=[O:51])[C@H:42]([CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[NH2:43])C.CN1CCOCC1.O.[OH-].[Li+]>C(Cl)Cl>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH:12]=[CH:13][CH:14]=[CH:15]3)=[CH:8][CH:9]=2)[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:3]1[C:22]([NH:43][C@H:42]([C:41]([OH:40])=[O:51])[CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[O:23]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 165085Ethyl L-phenylalaninate hydrochlorideHCID 168937Lithium hydroxide, monohydrateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 60007963HCID 60007963, compound

Product 1

HCID 11248247HCID 11248247, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-methyl-3-phenyl-5-(1H-pyrrol-1-yl)-1H-indole-2-carboxylic acid (0.28 g, 0.9 mmol), 1-[3-(dimethylamino)propyl-3-ethylcarbodiimide hydrochloride (0.29 g, 1.2 mmol), and L-phenylalanine ethyl ester hydrochloride (0.34 g, 1.5 mmol) was stirred in CH2Cl2 (15 mL). N-methylmorpholine (0.50 g, 5 mmol) was added and the mixture was stirred at room temperature for 3 h. The mixture was then washed with 0.05 N HCl and water. The resulting solution was dried with MgSO4 and concentrated. The residue was dissolved in 20 mL of 2:1:1 THF/MeOH/water and lithium hydroxide monohydrate (0.30 g, 7.1 mmol) was added. The reaction was stirred at room temperature for 1 day. Most of the organic solvents was removed and the reaction mixture was made acidic (pH 6) with glacial acetic acid, and the solid was collected and purified by semi-preparative HPLC (Column: Phenomenex C18 Luna 21.6 mm×60 mm, 5 μM; Solvent A: Water (0.1% TFA buffer); Solvent B: Acetonitrile (0.1% TFA buffer); Solvent Gradient: Time 0:0% B; 10 min: 100% B; Hold 100% B 5 min. Flow Rate: 22.5 mL/min). The product was collected based on UV absorption and concentrated to give the title compound as a white solid (0.25 g, 60%): 1H NMR (DMSO-d6) δ 2.91 (dd, J=13.9, 3.0 Hz, 1 H), 3.19 (dd, J=13.9, 4.0 Hz, 1 H), 3.59 (s, 3 H), 4.65-4.75 (m, 1 H), 6.22 (t, J=2.2 Hz, 2 H), 7.20-7.50 (m, 13 H), 7.60-7.68 (m, 2 H), 8.98 (d, J=8.1 Hz, 1 H), 12.94 (br s, 1 H); MS (ESI) m/z 464 (MH+); MS (ESI) m/z 462 ([M-H]−); HRMS calcd for C29H26N3O3: 464.1975; found (ESI+): 464.1959; Anal. calcd for C29H25N3O3: C, 75.14; H, 5.44; N, 9.07. Found: C, 74.72; H, 5.30; N, 8.93.

Workup

  1. washThe mixture was then washed with 0.05 N HCl and water
  2. dry with materialThe resulting solution was dried with MgSO4
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in 20 mL of 2:1:1 THF/MeOH/water
  5. stirringThe reaction was stirred at room temperature for 1 day
  6. customMost of the organic solvents was removed
  7. customthe solid was collected
  8. custompurified by semi-preparative HPLC (Column: Phenomenex C18 Luna 21.6 mm×60 mm, 5 μM; Solvent A: Water (0.1% TFA buffer); Solvent B: Acetonitrile (0.1% TFA buffer); Solvent Gradient: Time 0:0% B; 10 min: 100% B; Hold 100% B 5 min. Flow Rate: 22.5 mL/min)
  9. customThe product was collected
  10. custombased on UV absorption
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-4517de4e7e9643409b729e43535b0364
Source dataset
uspto-grants-2007_09
Patent number
US07265148B2

Reaction notes

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