Water → 1-[4-(4-Amino-6-vinylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-3-[4-(trifluoromethyl)pyridin-2-yl]urea

HRID 73714Notes

Reaction equation

HRID 73714 reaction equation
[CH3:1]C(C)([O-])C.[K+].[NH2:7][C:8]1[C:13]2=[C:14]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:28][C:29]4[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][N:30]=4)=[O:27])=[CH:21][CH:20]=3)[C:15]([CH:17]=O)=[CH:16][N:12]2[N:11]=[CH:10][N:9]=1.O>O1CCOCC1.[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:7][C:8]1[C:13]2=[C:14]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:28][C:29]4[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][N:30]=4)=[O:27])=[CH:21][CH:20]=3)[C:15]([CH:17]=[CH2:1])=[CH:16][N:12]2[N:11]=[CH:10][N:9]=1

Participants

6

Reactant 3

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 577581691-[4-(4-Amino-6-formylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-3-[4-(trifluoromethyl)pyridin-2-yl]urea

Product 1

HCID 577583301-[4-(4-Amino-6-vinylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-3-[4-(trifluoromethyl)pyridin-2-yl]urea

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

Potassium tert-butoxide (1.0 g, 9.06 mmol) was suspended in 1,4-dioxane (20 mL) and treated with methyltriphenylphosphonium bromide (3.2 g, 9.06 mmol). The mixture was allowed to stir at rt for 30 min. A yellow suspension formed then Intermediate AF (1-[4-(4-amino-6-formylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-3-[4-(trifluoromethyl)-pyridin-2-yl]urea) (2.0 g, 4.53 mmol) in 1,4-dioxane (10 mL) was slowly added and the reaction was stirred at rt for 4 hr. The reaction was slowly poured into vigorously stirring water. The mixture was allowed to stir for 1 hr. The solid was filtered and rinsed with water and MeOH. A light brown solid was isolated (1.2 g, 60%). 1H-NMR (DMSO-d6) δ 9.90 (s, 1H), 9.77 (s, 1H), 8.53 (d, J=5.2 Hz, 1H), 8.06-8.05 (m, 2H), 7.84 (s, 1H), 7.64 (d, J=8.5 Hz, 2H), 7.36 (d, J=5.4 Hz, 1H), 7.31 (d, J=8.5 Hz, 2H), 6.39 (dd, J1=11.3, J2=17.6 Hz, 1H), 5.63 (dd, J1=1.7, J2=17.5 Hz, 1H), 5.12 (dd, J1=1.5, J2=11.1 Hz, 2H). MS [M+H]+=440.0; LCMS RT=2.88.

Workup

  1. customA yellow suspension formed
  2. stirringthe reaction was stirred at rt for 4 hr
  3. stirringto stir for 1 hr
  4. filtrationThe solid was filtered
  5. washrinsed with water and MeOH
  6. customA light brown solid was isolated (1.2 g, 60%)
  7. customLCMS RT=2.88

Sources & evidence

ORD record
ord-e49e8d3f3f8d452ea11c8ef00e6d8045
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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