1-(2-Fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea → N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2,5-difluorophenyl}-N'-[2-fluoro-5-(trifluoromethyl)-phenyl]urea

HRID 73711Notes

Reaction equation

HRID 73711 reaction equation
Br[C:2]1[C:3]([CH3:19])=[C:4]([CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[N:5]2[C:10]=1[C:9]([NH2:11])=[N:8][CH:7]=[N:6]2.[F:20][C:21]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[C:24]([F:36])=[CH:23][C:22]=1[NH:37][C:38]([NH:40][C:41]1[CH:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[CH:43][C:42]=1[F:51])=[O:39].FC1C=CC(C(F)(F)F)=CC=1NC(NC1C=CC(B2OC(C)(C)C(C)(C)O2)=CC=1)=O>>[NH2:11][C:9]1[C:10]2=[C:2]([C:25]3[C:24]([F:36])=[CH:23][C:22]([NH:37][C:38]([NH:40][C:41]4[CH:46]=[C:45]([C:47]([F:48])([F:49])[F:50])[CH:44]=[CH:43][C:42]=4[F:51])=[O:39])=[C:21]([F:20])[CH:26]=3)[C:3]([CH3:19])=[C:4]([CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:5]2[N:6]=[CH:7][N:8]=1

Participants

4

Reactant 3

HCID 161252301-(2-Fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 579552405-Bromo-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 592319651-[2,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3-[2-fluoro-5-(trifluoromethyl)-phenyl]urea

Product 1

HCID 57955330N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2,5-difluorophenyl}-N'-[2-fluoro-5-(trifluoromethyl)-phenyl]ureaYield 14%

Procedure

The title compound was prepared in a manner similar to the procedure described for the preparation of Example 117 Step 4, using the product of step 1, Example 119 (5-bromo-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine) in place of 5-bromo-6-methyl-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine and Intermediate AAB (1-[2,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3-[2-fluoro-5-(trifluoromethyl)-phenyl]urea) in place of Intermediate AAN (1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea) 25 mg (14%) of the desired product was isolated. 1H-NMR (DMSO-d6) δ 9.51-9.45 (m, 2H), 8.63-8.61 (m, 1H), 8.20-8.13 (m, 1H), 7.87 (s, 1H), 7.55-7.48 (m, 1H), 7.45-7.39 (m, 1H), 7.33-7.27 (m, 1H), 3.80 (s, 2H), 3.53-3.50 (m, 4H), 2.41-2.39 (m, 4H), 2.03 (s, 3H); MS [M+H]+=580.1; LCMS RT=2.65.

Workup

  1. customThe title compound was prepared in a manner similar to the procedure
  2. customdescribed for the preparation of Example 117 Step 4
  3. customwas isolated
  4. customLCMS RT=2.65

Sources & evidence

ORD record
ord-6ead0e9c2f3b4787884097605fd1f5bd
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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