Ethyl Acetate → 2-methyl-5-{[(1R)-1-methylpropyl]amino}benzene-1,4-dicarboxamide

HRID 906056Notes

Reaction equation

HRID 906056 reaction equation
C[N:2](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]([C:28]1[C:36]([NH:37][C@H:38]([CH3:41])[CH2:39][CH3:40])=[CH:35][C:31]([C:32](O)=[O:33])=[C:30]([CH3:42])[CH:29]=1)=[O:27].C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>CN(C=O)C>[CH3:42][C:30]1[CH:29]=[C:28]([C:26]([NH2:25])=[O:27])[C:36]([NH:37][C@H:38]([CH3:41])[CH2:39][CH3:40])=[CH:35][C:31]=1[C:32]([NH2:2])=[O:33]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57748496(R)-5-(sec-butylamino)-4-(aminocarbonyl)-2-methylbenzoic acid

Product 1

HCID 709062132-methyl-5-{[(1R)-1-methylpropyl]amino}benzene-1,4-dicarboxamideYield 130.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of [6-(3-endo-amino-8-azabicyclo[3.2.1]oct-8-yl)pyridin-3-yl](cyclopropyl)methanone (100 mg, 0.37 mmol), HATU (210 mg, 0.55 mmol), 4-(aminocarbonyl)-2-methyl-5-{[(1R)-1-methylpropyl]amino}benzoic acid (synthesized in reagent preparation 41) (138 mg, 0.55 mmol), and diisopropylethyl-amine (256 μl, 1.47 mmol) in DMF (3 mL) was stirred at room temperature for 2 h. Concentration and column chromatography on silica (dichloromethane:methanol 100:0 then 95:5) followed by trituration of the residue obtained on concentration of the combined pure fractions with ethyl acetate afforded N-{8-[5-(cyclopropyl-carbonyl)pyridin-2-yl]-8-azabicyclo[3.2.1]oct-3-endo-yl}-2-methyl-5-{[(1R)-1-methylpropyl]amino}benzene-1,4-dicarboxamide (179 mg, 96% yield) as a pale yellow powder. 1H NMR (400 MHz, methanol-d4): 8.84 (d, 1H), 8.11 (dd, 1H), 7.45 (s, 1H), 6.78 (d, 1H), 6.68 (s, 1H), 4.68 (br s, 2H), 4.02 (t, 2H), 3.77-3.67 (m, 1H), 3.25-3.19 (m, 2H), 2.76-2.70 (m, 1H), 2.32-2.25 (m, 7H), 2.18-2.14 (m, 2H), 1.97 (br s, 1H), 1.70-1.59 (m, 1H), 1.60-1.50 (m, 1H), 1.25-1.18 (m, 4H), 1.12-1.09 (m, 2H), 1.06-1.01 (m, 2H), 0.97 (t, 3H); MS (EI) for C29H37N5O3: 504 (MH+).

Workup

  1. concentrationConcentration and column chromatography on silica (dichloromethane:methanol 100:0

Sources & evidence

ORD record
ord-0f82f4e0ce5a4669a1b1e8781bd13ab7
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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