Triethylamine → 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((dimethylamino)methyl)benzamide

HRID 449922Notes

Reaction equation

HRID 449922 reaction equation
C[CH2:2][N:3](CC)[CH2:4]C.N(C)C.Cl.[Cl:12][C:13]1[CH:33]=[C:32]([CH:34]=O)[CH:31]=[C:30]([Cl:36])[C:14]=1[C:15]([NH:17][C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])[CH:19]=1)=[O:16].[BH4-].[Na+]>CO.CCOC(C)=O>[Cl:36][C:30]1[CH:31]=[C:32]([CH2:34][N:3]([CH3:4])[CH3:2])[CH:33]=[C:13]([Cl:12])[C:14]=1[C:15]([NH:17][C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])[CH:19]=1)=[O:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 4311764Sodium borohydrideHCID 86648961HCID 86648961, compound

Product 1

HCID 596183342,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-((dimethylamino)methyl)benzamideYield 36.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Et3N (121 mg, 1.2 mmol) in absolute methanol (1 mL) was added Me2NH HCl (103 mg, 1.2 mmol), Ti(O-iPr)4 (114 mg, 0.40 mmol), and 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)-4-formylbenzamide (80 mg, 0.20 mmol). The reaction was stirred at room temperature for 9 hours and then NaBH4 (12 mg, 0.30 mmol) was added. The resulting mixture was stirred for 10 hours and then diluted with EtOAc (20 mL). The organic solution was washed with water (3×10 ml) and then concentrated under reduced pressure. The residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford the desired product (30 mg, 31% yield). 1H NMR (500 MHz, MeOH-d4): δ 8.31 (s, 1H), 8.24 (s, 1H), 7.60 (m, 1H), 7.48 (s, 2H), 3.52 (s, 2H), 2.28 (s, 6H), 1.91 (m, 1H), 1.02-0.98 (m, 2H), 0.94-0.90 (m, 2H). LCMS (ESI) m/z: 407.1 [M+H+].

Workup

  1. stirringThe resulting mixture was stirred for 10 hours
  2. washThe organic solution was washed with water (3×10 ml)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

Sources & evidence

ORD record
ord-4310987ddc8d4a4daebf0e87d8b4fd5a
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

Loading…