Methanesulfonic Acid → HCID 42598186, compound

HRID 1096479Notes

Reaction equation

HRID 1096479 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[N:29]=4)=[C:21]([F:36])[CH:20]=3)[C:9]([C:11]([NH:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[O:12])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1.[CH3:37][S:38]([OH:41])(=[O:40])=[O:39]>C1COCC1>[CH3:37][S:38]([OH:41])(=[O:40])=[O:39].[CH3:37][S:38]([OH:41])(=[O:40])=[O:39].[NH2:1][C:2]1[C:7]2=[C:8]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:35])[NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[N:29]=4)=[C:21]([F:36])[CH:20]=3)[C:9]([C:11]([NH:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[O:12])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 6395Methanesulfonic Acid2×HCID 42597459HCID 42597459, compound

Product 1

HCID 42598186HCID 42598186, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

To 4-amino-5-(3-fluoro-4-{[(6-methylpyridin-2-yl)carbamoyl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide (5.9 g) was added THF (650 mL). The mixture was heated until dissolution took place (up to 80° C.). In a separate flask methane sulfonic acid (2.5 mL) was diluted with THF (25 mL). 17 mL of the methane sulfonic acid solution in THF was added to the solution of 4-amino-5-(4-{[(6-methylpyridin-2-yl)carbamoyllamino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide in THF. The mixture was left to stir for 16 h. The solid was filtered using a 0.2 uM membrane filter. The solid was dried to give 7.91 g (97%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.68 (t, 1H), 8.60 (br s, 1H), 8.38 (t, 1H), 8.30 (s, 1H), 8.03 (s, 1H), 7.70 (t, 1H), 7.30 (d, 1H), 7.18 (d, 1H), 7.02 (bd, 1H), 6.85 (d, 1H), 3.98 (m, 2H), 2.54 (s, 3H), 2.32 (s, 6H); ES-MS m/z 503.30 (MH)+, HPLC RT (Method A) 2.64 min. DSC mp.=249.97° C. (after stirring in MeOH for 1 Week and drying mp.=258.99° C.) Anal. Calc'd for C22H18F4N8O2.2(CH4O3S): C, 41.50%; H, 3.77%; F, 10.94%; N, 16.13%; O, 18.43%; S, 9.23%. Found: C, 41.21%; H, 3.51%; N, 15.69%. Karl Fischer Titration: 0.96% water.

Workup

  1. temperatureThe mixture was heated until dissolution
  2. customup to 80° C.
  3. waitThe mixture was left
  4. filtrationThe solid was filtered
  5. filtrationfilter
  6. customThe solid was dried

Sources & evidence

ORD record
ord-706fe2c28f3e4174beaa9b5e0197a5fd
Source dataset
uspto-grants-2012_03
Patent number
US08138336B2

Reaction notes

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