Diisopropylethylamine → HCID 178474065, compound

HRID 1874840Notes

Reaction equation

HRID 1874840 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([NH:28][C:29]1[CH:40]=[CH:39][C:32]2[NH:33][C:34]([C:36]([OH:38])=O)=[N:35][C:31]=2[CH:30]=1)(=[O:27])[CH3:26].[NH2:41][CH2:42][C:43]1[C:44]([F:60])=[C:45]([O:50][C:51]2[CH:52]=[C:53]([CH:56]=[C:57]([Cl:59])[CH:58]=2)[C:54]#[N:55])[C:46]([Cl:49])=[CH:47][CH:48]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.O>[C:25]([NH:28][C:29]1[CH:40]=[CH:39][C:32]2[NH:33][C:34]([C:36]([NH:41][CH2:42][C:43]3[CH:48]=[CH:47][C:46]([Cl:49])=[C:45]([O:50][C:51]4[CH:52]=[C:53]([C:54]#[N:55])[CH:56]=[C:57]([Cl:59])[CH:58]=4)[C:44]=3[F:60])=[O:38])=[N:35][C:31]=2[CH:30]=1)(=[O:27])[CH3:26]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 178474067HCID 178474067, compound

Product 1

HCID 178474065HCID 178474065, compoundYield 8.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (0.092 g, 0.241 mmol) was added to a solution of 5-(acetylamino)-1H-benzimidazole-2-carboxylic acid (0.035 g, 0.161 mmol), 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.050 g, 0.161 mmol), and DIPEA (0.031 g, 0.241 mmol) in DMF (1 mL). After stirring at RT overnight, the reaction mixture was diluted with ethyl acetate and water. The organic layer was washed with water, dried over sodium sulfate and concentrated. The crude product was purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to give the title compound (0.007 g, 8.5%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 10.03 (s, 1H), 9.48 (s, 1H), 8.11 (m, 1H), 7.74-7.90 (m, 1H), 7.43-7.67 (m, 4H), 7.35-7.44 (m, 1H), 7.26-7.34 (m, 1H), 4.55 (s, 2H), 2.05 (s, 3H). MS: m/z 512 (M+1).

Workup

  1. washThe organic layer was washed with water
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA)

Sources & evidence

ORD record
ord-53eec98f751246a0a5a1bebef1e03d99
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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