2-Pyridinemethanamine → N-(tert-butyl)-2-(difluoromethyl)-5-(8-phenyl-1-((pyridin-2-ylmethyl)amino)pyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide

HRID 1478409Notes

Reaction equation

HRID 1478409 reaction equation
[C:1]([NH:5][S:6]([C:9]1[C:10]([CH:31]([F:33])[F:32])=[N:11][CH:12]=[C:13]([C:15]2[N:20]3[CH:21]=[CH:22][C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[C:19]3[C:18](Cl)=[N:17][N:16]=2)[CH:14]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH2:40][NH2:41]>>[C:1]([NH:5][S:6]([C:9]1[C:10]([CH:31]([F:33])[F:32])=[N:11][CH:12]=[C:13]([C:15]2[N:20]3[CH:21]=[CH:22][C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[C:19]3[C:18]([NH:41][CH2:40][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][N:34]=3)=[N:17][N:16]=2)[CH:14]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 195092-PyridinemethanamineHCID 90423731N-(tert-butyl)-5-(1-chloro-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)-2-(difluoromethyl)pyridine-3-sulfonamide

Product 1

HCID 90425044N-(tert-butyl)-2-(difluoromethyl)-5-(8-phenyl-1-((pyridin-2-ylmethyl)amino)pyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamideYield 62.1%

Procedure

A solution of N-(tert-butyl)-5-(1-chloro-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)-2-(difluoromethyl)pyridine-3-sulfonamide (0.050 g, 0.10 mmol) in pyridin-2-ylmethanamine (0.110 g, 1.02 mmol) was heated in a sealed tube at 100° C. for 6 h. The volatile components were removed under reduced pressure and the resulting residue was purified by CombiFlash Isco (REDISEP®, SiO2, 24 g, 0-60% EtOAc/petroleum ether) to obtain N-(tert-butyl)-2-(difluoromethyl)-5-(8-phenyl-1-((pyridin-2-ylmethyl)amino)pyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide (0.035 g, 61%) as a brown solid. LCMS Method B-4: retention time 1.12 min, [M+1]=564.5. 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.18 (s, 9H), 4.63 (d, J=6.0 Hz, 2H), 6.61 (dd, J=4.4 Hz, J=6.0 Hz, 1H), 6.98 (d, J=2.8 Hz, 1H), 7.33-7.70 (m, 8H), 7.72 (d, J=2.8 Hz, 1H), 7.98-8.05 (m, 1H), 8.32 (d, J=4.8 Hz, 1H), 8.35 (s, 1H), 8.80 (br s, 1H), 9.41 (d, J=2.0 Hz, 1H).

Workup

  1. customThe volatile components were removed under reduced pressure
  2. customthe resulting residue was purified by CombiFlash Isco (REDISEP®, SiO2, 24 g, 0-60% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-4f6db5bec8b740b2847882bcc0fb2925
Source dataset
uspto-grants-2016_08
Patent number
US09403834B2

Reaction notes

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