Methanesulfonic Acid → HCID 59548172, compound

HRID 1621611Notes

Reaction equation

HRID 1621611 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([CH2:32][N:33]4[CH2:38][CH2:37][N:36]([C:39]([N:41]([CH3:43])[CH3:42])=[O:40])[CH2:35][CH2:34]4)[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=3)[N:10]=2)=CC=1.C(O)(C(F)(F)F)=O.CS(O)(=O)=O>>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[CH:17]=[C:18]([CH2:32][N:33]3[CH2:38][CH2:37][N:36]([C:39]([N:41]([CH3:43])[CH3:42])=[O:40])[CH2:35][CH2:34]3)[CH:19]=[N:20][C:21]=2[NH:22][C:23]2[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=2)[N:10]=1

Participants

4

Reactant 3

HCID 6395Methanesulfonic AcidHCID 6422Trifluoroacetic acidHCID 66611087HCID 66611087, compound

Product 1

HCID 59548172HCID 59548172, compoundYield 36.7%

Conditions

Temperature
85 °C

Procedure

A stirred mixture of 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)-N,N-dimethylpiperazine-1-carboxamide (0.3555 g, 0.482 mmol) in TFA (1.859 mL, 24.12 mmol) was treated with methanesulfonic acid (0.031 mL, 0.482 mmol) and the solution was heated at 85° C. overnight. After cooling, the residue was carefully concentrated and diluted with 5% MeOH/DCM w/NH3. The solution was concentrated with SiO2 and chromatographed through a Redi-Sep pre-packed silica gel column (pure DCM to 10% MeOH in DCM) to give 4-((5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)-N,N-dimethylpiperazine-1-carboxamide (88 mg, 0.177 mmol, 36.7% yield). 1H NMR (400 MHz, d6-DMSO) δ 12.04 (s, 1H); 8.92 (br. s., 1H); 8.45 (s, 1H); 8.40 (br. s., 1H); 8.33 (d, J=11.35 Hz, 1H); 7.96 (br. s., 1H); 7.87 (br. s., 1H); 4.40 (br. s., 2H); 3.95 (s, 3H); 3.64 (d, J=14.87 Hz, 2H); 3.25-3.35 (m, 2H); 2.88-3.15 (m, 4H); 2.78 (s, 6H); 2.44 (s, 3H). m/z (ESI, +ve ion) 497.1 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. concentrationthe residue was carefully concentrated
  3. additiondiluted with 5% MeOH/DCM
  4. concentrationThe solution was concentrated with SiO2
  5. customchromatographed through a Redi-Sep pre-packed silica gel column (pure DCM to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-40efc7cbd5134deeb6fdc46907cf3212
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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