Dimethylamine → N-cyclopropyl-3-{[4-({5-[(dimethylamino)methyl]pyridin-2-yl}methoxy)benzoyl]amino}-4-methylbenzamide

HRID 550073Notes

Reaction equation

HRID 550073 reaction equation
[CH:1]1([NH:4][C:5](=[O:32])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:31])[C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([CH2:29]O)=[CH:25][N:24]=4)=[CH:17][CH:16]=3)[CH:7]=2)[CH2:3][CH2:2]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:55][NH:56][CH3:57].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C.O>[CH:1]1([NH:4][C:5](=[O:32])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:31])[C:15]3[CH:16]=[CH:17][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([CH2:29][N:56]([CH3:57])[CH3:55])=[CH:25][N:24]=4)=[CH:19][CH:20]=3)[CH:7]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 674DimethylamineHCID 159087TriacetoxyperiodinaneHCID 5049666Sodium triacetoxyborohydrideHCID 11304999HCID 11304999, compound

Product 1

HCID 11305666N-cyclopropyl-3-{[4-({5-[(dimethylamino)methyl]pyridin-2-yl}methoxy)benzoyl]amino}-4-methylbenzamideYield 28.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 962WaterCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To N-cyclopropyl-3-[(4-{[5-(hydroxymethyl)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide (100 mg, 0.232 mmol) in DCM (10 mL) was added Dess-Martin periodinane (197 mg, 0.464 mmol) and the reaction was stirred at room temperature for 3 h. The reaction was diluted with DCM (40 mL), washed with 2N NaOH (3×15 mL) and then a saturated brine solution (20 mL). The DCM solution of the aldehyde was dried with magnesium sulphate and then concentrated under reduced pressure to approximately 10 mL. To this solution was added dimethylamine (2M in THF, 0.13 mL, 0.260 mmol), acetic acid (2 drops) and titanium iso-propoxide (132 mg, 0.464 mmol). The mixture was stirred at room temperature for 1 h and then sodium triacetoxyborohydride (123 mg, 0.580 mmol) was added. The reaction was stirred for 18 h at room temperature. Water (4 drops) was added and the reaction was evaporated to dryness. The residue was purified by basic preparative HPLC to give the title compound as a white solid (30 mg, 28%); NMR Spectrum: (DMSOd6) 0.62 (m, 2H), 0.75 (m, 2H), 2.21 (s, 6H), 2.31 (s, 3H), 2.90 (m, 1H), 3.48 (s, 2H), 5.83 (s, 2H), 7.22 (d, 2H), 7.38 (d, 1H), 7.57 (d, 1H), 7.68 (dd, 1H), 7.81 (m, 1H), 7.85 (d, 1H), 8.04 (d, 2H), 8.42 (d, 1H), 8.57 (s, 1H), 9.88 (s, 1H); Mass Spectrum: M+H+ 459.

Workup

  1. washwashed with 2N NaOH (3×15 mL)
  2. dry with materialThe DCM solution of the aldehyde was dried with magnesium sulphate
  3. concentrationconcentrated under reduced pressure to approximately 10 mL
  4. stirringThe mixture was stirred at room temperature for 1 h
  5. stirringThe reaction was stirred for 18 h at room temperature
  6. customthe reaction was evaporated to dryness
  7. customThe residue was purified by basic preparative HPLC

Sources & evidence

ORD record
ord-5ac1fddf8f2e4d71a8e1546d9df58fa2
Source dataset
uspto-grants-2011_05
Patent number
US07943776B2

Reaction notes

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