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

HRID 403037Notes

Reaction equation

HRID 403037 reaction equation
[CH:1]1([NH:4][C:5](=[O:37])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:36])[C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26](OCC5OCCO5)=[CH:25][N:24]=4)=[CH:17][CH:16]=3)[CH:7]=2)[CH2:3][CH2:2]1.Cl.[OH-].[Na+].[CH3:41][NH:42][CH3:43].C(O[BH-](O[C:54](=[O:56])[CH3:55])OC(=O)C)(=O)C.[Na+]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:1]1([NH:4][C:5](=[O:37])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:36])[C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([O:56][CH2:54][CH2:55][N:42]([CH3:43])[CH3:41])=[CH:25][N:24]=4)=[CH:17][CH:16]=3)[CH:7]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 14798Sodium Hydroxide2×HCID 5049666Sodium triacetoxyborohydrideHCID 11488985N-cyclopropyl-3-[(4-{[5-(1,3-dioxolan-2-ylmethoxy)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide

Product 1

HCID 11431784N-cyclopropyl-3-{[4-({5-[2-(dimethylamino)ethoxy]pyridin-2-yl}methoxy)benzoyl]amino}-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of N-cyclopropyl-3-[(4-{[5-(1,3-dioxolan-2-ylmethoxy)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide (1.0 g, 2 mmol) in methanol (20 mL) was added hydrochloric acid (36% aqueous solution, 10 mL). After 2 hours the solution was basified by addition of 2N sodium hydroxide (55 mL). The precipitate was filtered off and dissolved in THF (100 mL), then stirred while adding a solution of dimethylamine (2M in THF, 2 mL, 4 mmol), titanium isopropoxide (3 mL, 10 mmol) and sodium triacetoxyborohydride (2.2 g, 10 mmol). After 16 hours the mixture was basified with 2N sodium hydroxide, stirred for 10 minutes and the top layer decanted. The lower layer was stirred with THF (50 mL) and decanted again, the combined top layers were dried over magnesium sulphate. The title compound was isolated by chromatography on silica, eluting with a gradient of 0-30% methanol in ethyl acetate to give a gum (120 mg); NMR Spectrum: (CDCl3) 0.60 (m, 2H), 0.83 (m, 2H), 2.32 (s, 3H), 2.40 (s, 6H), 2.82 (t, 2H), 2.90 (m, 1H), 4.17 (t, 2H), 5.20 (s, 2H), 6.60 (s, 1H), 7.06 (d, 2H), 7.26 (dd, 2H), 7.42 (d, 1H), 7.56 (d, 1H), 7.86 (d, 2H), 7.90 (s, 1H), 8.10 (s, 1H), 8.32 (s, 1H); Mass Spectrum: M+H+ 489.

Workup

  1. filtrationThe precipitate was filtered off
  2. dissolutiondissolved in THF (100 mL)
  3. stirringstirred for 10 minutes
  4. customthe top layer decanted
  5. stirringThe lower layer was stirred with THF (50 mL)
  6. customdecanted again
  7. dry with materialthe combined top layers were dried over magnesium sulphate

Sources & evidence

ORD record
ord-2109f3f5de8e4d0d9a2398793af52ba3
Source dataset
uspto-grants-2014_06
Patent number
US08742124B2

Reaction notes

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