Diisopropylethylamine → HCID 66740597, compound

HRID 1627265Notes

Reaction equation

HRID 1627265 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:20])[CH3:19])=[CH:16][N:17]=1)[C:5]([OH:7])=O.[NH2:38][C@@H:39]([CH2:47][CH2:48][CH2:49][NH:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:54]([O:53][C:51]([NH:50][CH2:49][CH2:48][CH2:47][C@H:39]([NH:38][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([F:37])[C:10]([CH2:11][S:12][C:13]2[N:14]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:15]([C:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=3)([CH3:20])[CH3:19])=[CH:16][N:17]=2)=[C:2]([Cl:1])[CH:3]=1)[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[O:52])([CH3:56])([CH3:57])[CH3:55]

Participants

6

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 16079671HCID 16079671, compoundHCID 667398303-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluoro-phenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid

Product 1

HCID 66740597HCID 66740597, compoundYield 80.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 0° C. solution of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluoro-phenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid (0.94 g, 0.17 mmol), (S)-tert-butyl 2-amino-5-(tert-butoxycarbonylamino)pentanoate (0.050 g, 0.18 mmol) and HATU (0.067 g, 0.18 mmol) in DMF (4 mL) was added DIPEA (0.058 mL, 0.33 mmol). The ice bath was removed and the reaction was stirred for 2 h at room temperature. The reaction was quenched with satd NaHCO3 and diluted with EtOAc. The organic layer was washed with H2O (2×5 mL), brine, and dried with Na2SO4. The solvent was removed in vacuo and the residue was purified by column chromatography to afford 114 mg of (S)-tert-butyl 5-(tert-butoxycarbonylamino)-2-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)pentanoate. The compound was then dissolved in 4N solution of HCl in dioxane and stirred for 2 h, when the reaction was determined to be complete by LCMS. Ether was added to the reaction mixture. Then the solids were collected by filtration and dried under vacuum to afford the title compound (75 mg). 1H-NMR (DMSO6, 400 MHz) δ 9.00 (d, J=8.3 Hz, 1H), 8.01 (s, 3H), 7.93 (s, 1H), 7.82-7.75 (m, 2H), 7.23 (d, J=8.5 Hz, 1H), 7.06-6.99 (m, 2H), 6.67-6.64 (m, 1H), 6.61-6.57 (m, 1H), 6.53-6.52 (m, 1H), 6.50-6.47 (m, 1H), 4.43-4.38 (m, 1H), 4.19 (s, 2H), 3.70 (s, 3H), 2.84-2.80 (m, 2H), 1.97-1.80 (m, 2H), 1.75-1.66 (m, 2H), 1.51 (m, 6H); MS (ES): 677 [M]+.

Workup

  1. customThe ice bath was removed
  2. customThe reaction was quenched with satd NaHCO3
  3. additiondiluted with EtOAc
  4. washThe organic layer was washed with H2O (2×5 mL), brine
  5. dry with materialdried with Na2SO4
  6. customThe solvent was removed in vacuo
  7. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-cc539766c8b04450b54207ba9a4ae9b1
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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