Imidazole → HCID 89649393, compound

HRID 2274591Notes

Reaction equation

HRID 2274591 reaction equation
[CH2:1]([N:5]([CH2:37][CH2:38][CH2:39][CH3:40])[C:6]([C:8]1[CH:12]=[C:11]([CH3:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:15]=2[C:23]([N:25]2[C@H:34]([CH2:35][OH:36])[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].[Si:41](Cl)([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42].N1C=CN=C1>C(Cl)Cl.O>[CH2:37]([N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]([C:8]1[CH:12]=[C:11]([CH3:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:15]=2[C:23]([N:25]2[C@H:34]([CH2:35][O:36][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[N:9]=1)=[O:7])[CH2:38][CH2:39][CH3:40]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 89660113HCID 89660113, compound

Product 1

HCID 89649393HCID 89649393, compoundYield 64.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)—N,N-dibutyl-1-(2-(3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-nitrophenyl)-5-methyl-1H-pyrazole-3-carboxamide (9.0 g, 16.4 mmol) in DCM (150 mL) were added TBDMS-chloride (2.98 g, 19.7 mmol), imidazole (2.23 g, 32.9 mmol) followed by stirring at RT for 12 h. The reaction mixture was diluted with water and extracted with EtOAc (300 mL×2), twice. The combined organic layers were washed with water (300 mL), brine (100 mL), dried over sodium sulphate and concentrated invacuo. The residue was purified on silica gel (100-200 mesh) to afford the title compound as a liquid 7 g (64%). Rf=0.74 (25% EtOAc in hexane); 1H NMR (400 MHz, DMSO-d6): δ 8.60-8.20 (m, 2H), 8.05-7.80 (m, 1H), 7.40-6.80 (m, 4H), 6.60-6.30 (m, 1H), 5.10-3.84 (m, 4H), 3.82-2.40 (m, 7H), 2.40-2.20 (m, 3H), 1.60-0.55 (m, 23H), 0.05-−0.40 (m, 6H); LC-MS: m/z 662.4 (M+H).

Workup

  1. extractionextracted with EtOAc (300 mL×2)
  2. washThe combined organic layers were washed with water (300 mL), brine (100 mL)
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated invacuo
  5. customThe residue was purified on silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-a255a5b47adf44c4a1a4750b99c58004
Source dataset
uspto-grants-2015_09
Patent number
US09126979B2

Reaction notes

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