Diisopropylethylamine → HCID 178494103, compound

HRID 470363Notes

Reaction equation

HRID 470363 reaction equation
C(N(CC)C(C)C)(C)C.[NH2:10][CH2:11][CH2:12][C:13]1[N:17]=[CH:16][NH:15][CH:14]=1.[F:18][C:19]1[C:20]([C:43](O)=[O:44])=[CH:21][C:22]2[N:26]=[C:25]([C:27]3[CH:32]=[C:31]([C:33]4[C:34]([O:39][CH3:40])=[N:35][CH:36]=[CH:37][CH:38]=4)[CH:30]=[CH:29][C:28]=3[OH:41])[NH:24][C:23]=2[CH:42]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.CN(C=O)C>[F:18][C:19]1[C:20]([C:43]([NH:10][CH2:11][CH2:12][C:13]2[N:17]=[CH:16][NH:15][CH:14]=2)=[O:44])=[CH:21][C:22]2[N:26]=[C:25]([C:27]3[CH:32]=[C:31]([C:33]4[C:34]([O:39][CH3:40])=[N:35][CH:36]=[CH:37][CH:38]=4)[CH:30]=[CH:29][C:28]=3[OH:41])[NH:24][C:23]=2[CH:42]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 136106361HCID 136106361, compoundHCID 178419017HCID 178419017, compound

Product 1

HCID 178494103HCID 178494103, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

N,N-Diisopropylethylamine (4.6 mL, 26.4 mmol) and histamine.2HCl (1.16 g, 6.3 mmol) were successively added to a solution of acid 9a (2.3 g, 6 mmol) and HBTU (2.5 g, 6.6 mmol) in THF (70 mL) and DMF (35 mL). The reaction mixture was stirred at room temperature for 18 h and the solvent was evaporated in vacuo. Water (35 mL) was added to the residue and the fine precipitate was collected by filtration and suspended in methanol/water (1/1, 100 mL). The suspension was stirred at room temperature for 14 h and the solid was collected by filtration and dried in vacuo at 40° C. for 14 h to afford the desired 6-fluoro-N-[2-(1H-imidazol-4-yl)ethyl]-2-[2-hydroxy-5-(2-methoxypyridin-3-yl)phenyl] 1H-benzimidazole-5-carboxamide (10a) as a colorless solid. 1H NMR (DMSO-d6) δ 13.79-11.28 (br s, 2H), 8.45-8.16 (m, 3H), 7.94-7.91 (m, 2H), 7.69-7.51 (m, 3H), 7.17-7.11 (m, 2H), 6.88 (s, 1H), 3.92 (s, 3H), 3.59-3.48 (m, 2H), 2.79 (t, J=6.6 Hz, 2H). ES-MS MH+ 473.48. EA was in agreement with the formula C25H21FN6O3.0.75H2O.

Workup

  1. customthe solvent was evaporated in vacuo
  2. additionWater (35 mL) was added to the residue
  3. filtrationthe fine precipitate was collected by filtration
  4. stirringThe suspension was stirred at room temperature for 14 h
  5. filtrationthe solid was collected by filtration
  6. customdried in vacuo at 40° C. for 14 h

Sources & evidence

ORD record
ord-8f2ff0b63e164003aea36a6fb2a1d3df
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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