N,N-Dimethylglycine → N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-[(N,N-dimethylglycyl)amino]-1H-indole-2-carboxamide

HRID 1875018Notes

Reaction equation

HRID 1875018 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl-].FC(F)(F)C(O)=O.[NH2:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[NH:42][C:41]([C:46]([NH:48][CH2:49][C:50]1[CH:55]=[CH:54][C:53]([Cl:56])=[C:52]([O:57][C:58]3[CH:63]=[C:62]([C:64]#[N:65])[CH:61]=[C:60]([Cl:66])[CH:59]=3)[C:51]=1[F:67])=[O:47])=[CH:40]2.[CH3:68][N:69]([CH3:74])[CH2:70][C:71](O)=[O:72].C(N(C(C)C)CC)(C)C>CN(C=O)C.CCOC(C)=O.O>[Cl:56][C:53]1[CH:54]=[CH:55][C:50]([CH2:49][NH:48][C:46]([C:41]2[NH:42][C:43]3[C:39]([CH:40]=2)=[CH:38][C:37]([NH:36][C:71](=[O:72])[CH2:70][N:69]([CH3:74])[CH3:68])=[CH:45][CH:44]=3)=[O:47])=[C:51]([F:67])[C:52]=1[O:57][C:58]1[CH:63]=[C:62]([C:64]#[N:65])[CH:61]=[C:60]([Cl:66])[CH:59]=1

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 866448845-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetateHCID 131720136BOP chloride

Product 1

HCID 59451476N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-[(N,N-dimethylglycyl)amino]-1H-indole-2-carboxamideYield 28%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

BOP chloride (0.079 g, 0.309 mmol) was added to a solution of 5-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate (0.060 g, 0.103 mmol), N,N-dimethylglycine (0.011 g, 0.103 mmol) and diisopropylethylamine (0.090 mL, 0.514 mmol) in DMF (1 mL). The mixture was stirred at RT for 1 hr. The reaction mixture was diluted with EtOAc and water. The organic layer was washed with water, dried over sodium sulfate, filtered and concentrated. The residue was triturated with methanol and dried under vacuum to give the title compound (0.016 g, 28%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.51 (br. s., 1H), 9.52 (br. s., 1H), 8.96 (t, 1H), 7.94 (s, 1H), 7.78 (s, 1H), 7.41-7.54 (m, 2H), 7.36 (t, 1H), 7.30 (s, 2H), 7.07 (s, 1H), 4.53 (d, 2H), 2.22 (s, 6H). ES MS: m/z 553 (M).

Workup

  1. washThe organic layer was washed with water
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was triturated with methanol
  6. customdried under vacuum

Sources & evidence

ORD record
ord-5f28cdadb5ad43379a4102ca71a0e0d3
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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