Imidazole → HCID 89660236, compound

HRID 2274598Notes

Reaction equation

HRID 2274598 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][C:10]([C:14]([N:16]([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:17][CH2:18][CH2:19][CH3:20])=[O:15])=[N:9]2)=[C:4]([C:25]([N:27]2[C@H:36]([CH2:37][OH:38])[CH2:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:28]2)=[O:26])[CH:3]=1.[Si:39](Cl)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40].N1C=CN=C1>C(Cl)Cl.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][C:10]([C:14]([N:16]([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:17][CH2:18][CH2:19][CH3:20])=[O:15])=[N:9]2)=[C:4]([C:25]([N:27]2[C@H:36]([CH2:37][O:38][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])[CH2:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:28]2)=[O:26])[CH:3]=1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 89650481HCID 89650481, compound

Product 1

HCID 89660236HCID 89660236, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-1-(4-bromo-2-(3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-5-methyl-1H-pyrazole-3-carboxamide (3.0 g, 5.2 mmol) in DCM (30 mL) were added TBDMS-chloride (0.93 g, 6.2 mmol), imidazole (0.70 g, 10.3 mmol) followed by stirring at RT for 5 h. The reaction mixture was diluted with water, extracted with EtOAc (100 mL×2), twice. The combined organic layers were washed with water (100 mL), brine (50 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 3.0 g (83%). Rf=0.66 (50% EtOAc in hexane); 1H NMR (400 MHz, DMSO-d6): δ 8.00-7.40 (m, 3H), 7.30-6.60 (m, 4H), 6.55-6.20 (m, 1H), 5.00-4.10 (m, 2H), 4.10-2.40 (m, 6H), 2.40-2.00 (m, 6H), 1.60-0.50 (m, 23H), 0.20-−0.40 (m, 6H); LC-MS: m/z 695.3 (M+H).

Workup

  1. extractionextracted with EtOAc (100 mL×2)
  2. washThe combined organic layers were washed with water (100 mL), brine (50 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-fec5129c228b4f76b8604ed5e6167d53
Source dataset
uspto-grants-2015_09
Patent number
US09126979B2

Reaction notes

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