Acryloyl chloride → HCID 118250870, compound

HRID 2283478Notes

Reaction equation

HRID 2283478 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([NH:6][C:7]2[C:12](=[O:13])[NH:11][CH:10]=[C:9]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([C:20]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([CH:29]([CH3:31])[CH3:30])=[C:25]([CH3:32])[CH:24]=4)=[O:21])[CH:15]=3)[CH:8]=2)[CH2:3]1.[C:33]([Cl:37])(=[O:36])[CH:34]=[CH2:35]>C(Cl)Cl>[ClH:37].[C:33]([N:2]1[CH2:5][CH:4]([NH:6][C:7]2[C:12](=[O:13])[NH:11][CH:10]=[C:9]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([C:20]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([CH:29]([CH3:30])[CH3:31])=[C:25]([CH3:32])[CH:24]=4)=[O:21])[CH:15]=3)[CH:8]=2)[CH2:3]1)(=[O:36])[CH:34]=[CH2:35]

Participants

4

Reactant 2

HCID 13140Acryloyl chlorideHCID 118250929HCID 118250929, compound

Product 1

HCID 118250870HCID 118250870, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(azetidin-3-ylamino)-N-(4-isopropyl-3-methylphenyl)-6-oxo-1,6-dihydro-[3,4′-bipyridine]-2′-carboxamide hydrochloride (60 mg, 0.14 mmol) in DCM (20 mL) was added acryloyl chloride (0.14 mL, 0.17 mmol) and TEA (0.1 mL, 0.7 mmol)). The mixture was stirred overnight at RT. The reaction was quenched by addition of MeOH (2 mL) and 4M HCl in 1,4-dioxane (2 mL). Water was added, the mixture extracted several times with ethyl acetate, the organic layers dried (MgSO4), filtered and concentrated. The residue was purified by Prep. HPLC (pH<7) and converted to the HCl salt to afford 5-((1-acryloylazetidin-3-yl)amino)-N-(4-isopropyl-3-methylphenyl)-6-oxo-1,6-dihydro-[3,4′-bipyridine]-2′-carboxamide hydrochloride (16 mg, 24% yield) as a yellow solid: 1H NMR (400 MHz, MeOD) δ 8.70 (d, J=4.8 Hz, 1H), 8.37 (d, J=1.2 Hz, 1H), 7.81 (dd, J=1.6, 5.2 Hz, 1H), 7.52 (s, 1H), 7.47 (s, 1H), 7.41 (d, J=1.6 Hz, 1H), 6.92 (s, 1H), 6.74 (d, J=2.4 Hz, 1H), 6.41 (dd, J=10.0, 16.8 Hz, 1H), 6.28 (dd, J=2.0, 16.8 Hz, 1H), 5.78 (dd, J=2.0, 10 Hz, 1H), 4.78-4.81 (m, 1H), 4.52-4.59 (m, 2H), 4.23-4.27 (m, 1H), 4.02-4.04 (m, 1H), 2.90-2.94 (m, 1H), 2.38 (s, 3H), 1.29 (d, J=6.8 Hz, 6H); MS (ES) m/z 472 (M+H).

Workup

  1. customThe reaction was quenched by addition of MeOH (2 mL) and 4M HCl in 1,4-dioxane (2 mL)
  2. additionWater was added
  3. extractionthe mixture extracted several times with ethyl acetate
  4. dry with materialthe organic layers dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Prep

Sources & evidence

ORD record
ord-6125a1fe5cc94faeb4c95ded1a08c69f
Source dataset
uspto-grants-2015_09
Patent number
US09145393B2

Reaction notes

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