N-(3-cyanopyridin-2-yl)-N-methylmethanesulfonamide → N-(3-(aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamide

HRID 1889859Notes

Reaction equation

HRID 1889859 reaction equation
[C:1]([C:3]1[C:4]([N:9]([CH3:14])[S:10]([CH3:13])(=[O:12])=[O:11])=[N:5][CH:6]=[CH:7][CH:8]=1)#[N:2].[H][H].Br[C:18]1[C:19]2[N:20]([N:24]=[C:25]([Cl:27])[N:26]=2)[CH:21]=[CH:22][CH:23]=1.[NH2:28][CH2:29][C:30]1[C:31]([N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])=[N:32][CH:33]=[CH:34][CH:35]=1>[Pd].N.CO>[NH2:2][CH2:1][C:3]1[C:4]([N:9]([CH3:14])[S:10]([CH3:13])(=[O:12])=[O:11])=[N:5][CH:6]=[CH:7][CH:8]=1.[Cl:27][C:25]1[N:26]=[C:19]2[C:18]([NH:28][CH2:29][C:30]3[C:31]([N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])=[N:32][CH:33]=[CH:34][CH:35]=3)=[CH:23][CH:22]=[CH:21][N:20]2[N:24]=1

Participants

9

Reactant 4

HCID 12568879N-(3-cyanopyridin-2-yl)-N-methylmethanesulfonamideHCID 45480403N-(3-(aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamideHCID 674813708-Bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridineHCID 178418361HCID 178418361, compound2×

Product 2

HCID 45480403N-(3-(aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamideHCID 67478948N-{3-[(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-pyridin-2-yl}-N-methyl-methanesulfonamide

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 222AmmoniaSolventHCID 887MethanolSolvent

Procedure

N-(3-Aminomethyl-pyridin-2-yl)-N-methyl-methanesulfonamide was prepared from N-(3-cyano-pyridin-2-yl)-N-methyl-methanesulfonamide (3.35 g, 15.8 mmol)(prepared as described in J. Heterocyclic Chemistry, 1979, 16, 1361-1363) via hydrogenation using a Paar apparatus with 10% palladium on carbon (50% Wet)(5:45:50, Palladium:carbon black:Water, 5.71 g, 2.68 mmol) and hydrogen (50 psi) in 7M ammonia in methanol (100 mL). The mixture was shaken on a Paar apparatus until adsorption of hydrogen ceased. The mixture was degassed, backflushed with nitrogen, filtered through a plug of diatomaceous earth and rinsed with dichloromethane. The filtrate was evaporated under reduced pressure. Product isolated as pale yellow oil (3.20, 93%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.37 (dd, J=4.6, 1.7 Hz, 1H), 7.92 (dd, J=7.7, 1.7 Hz, 1H), 7.32 (dd, J=7.7, 4.8 Hz, 1H), 4.04 (s, 2H), 3.26 (s, 3H), 3.08 (s, 3H). MS=216 (MH)+. 122b) N-{3-[(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-pyridin-2-yl}-N-methyl-methanesulfonamide was prepared from 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (100.0 mg, 0.4302 mmol) and N-(3-aminomethyl-pyridin-2-yl)-N-methyl-methanesulfonamide (102.0 mg, 0.4738 mmol) in a manner analogous to Example 2d. Product isolated as a tan solid (0.056 g, 35%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.43 (d, J=4.6 Hz, 1H), 8.11 (d, J=6.5 Hz, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.40-7.32 (m, 2H), 6.93 (t, J=7.5 Hz, 1H), 6.26 (d, J=7.9 Hz, 1H), 4.62 (d, J=6.3, 2H), 3.24 (s, 3H), 3.16 (s, 3H). MS=367, 369 (MH)+. 122c) N-Methyl-N-[3-({2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-methyl)-pyridin-2-yl]-methanesulfonamide was prepared from N-{3-[(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-pyridin-2-yl}-N-methyl-methanesulfonamide (75.0 mg, 0.204 mmol) and 4-(4-methyl-piperazin-1-yl)-phenylamine (47.0 mg, 0.246 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a brown foam (0.030 g, 28%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.40 (dd, J=4.7, 1.6 Hz, 1H), 7.84 (d, J=7.7 Hz, 1H), 7.80 (d, J=6.7 Hz, 1H), 7.48 (d, J=8.9 Hz, 2H), 7.29-7.24 (m, 1H), 6.96 (d, J=8.9 Hz, 2H), 6.63 (t, J=7.4 Hz, 1H), 6.56 (s, 1H), 6.28 (d, J=7.6 Hz, 1H), 5.28 (t, J=6.2 Hz, 1H), 4.76 (d, J=6.3 Hz, 2H), 3.32 (s, 3H), 3.18-3.13 (m, 4H), 3.09 (s, 3H), 2.62-2.57 (m, 4H), 2.36 (s, 3H). MS=522 (MH)+.

Workup

  1. customThe mixture was degassed
  2. filtrationfiltered through a plug of diatomaceous earth
  3. washrinsed with dichloromethane
  4. customThe filtrate was evaporated under reduced pressure
  5. customProduct isolated as pale yellow oil (3.20, 93%)

Sources & evidence

ORD record
ord-67687081333b43998d797bd8d03f602b
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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