1-trityl-4-vinyl-1H-imidazole → N-(4-fluoro-3-methoxybenzyl)-2-methyl-6-(5-(1-trityl-1H-imidazol-4-yl)-4,5-dihydroisoxazol-3-yl)pyrimidine-4-carboxamide

HRID 572652Notes

Reaction equation

HRID 572652 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:15]=[C:14]([CH:16]=[N:17][OH:18])[N:13]=[C:12]([CH3:19])[N:11]=2)=[O:9])=[CH:4][C:3]=1[O:22][CH3:23].[C:24]([N:43]1[CH:47]=[C:46]([CH:48]=[CH2:49])[N:45]=[CH:44]1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.Cl[O-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:15]=[C:14]([C:16]3[CH2:49][CH:48]([C:46]4[N:45]=[CH:44][N:43]([C:24]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)[CH:47]=4)[O:18][N:17]=3)[N:13]=[C:12]([CH3:19])[N:11]=2)=[O:9])=[CH:4][C:3]=1[O:22][CH3:23]

Participants

5

Reactant 3

HCID 113021301-trityl-4-vinyl-1H-imidazoleHCID 23665760Sodium HypochloriteHCID 136413230N-(4-fluoro-3-methoxybenzyl)-6-((hydroxyimino)methyl)-2-methylpyrimidine-4-carboxamide

Product 1

HCID 86675909N-(4-fluoro-3-methoxybenzyl)-2-methyl-6-(5-(1-trityl-1H-imidazol-4-yl)-4,5-dihydroisoxazol-3-yl)pyrimidine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a cold solution of N-(4-fluoro-3-methoxybenzyl)-6-((hydroxyimino)methyl)-2-methylpyrimidine-4-carboxamide (0.2 g, 0.628 mmol, Preparation #9,) and 1-trityl-4-vinyl-1H-imidazole (Organic Letters 2001, 3, 1319-1322) in DCM (20 mL) was added sodium hypochlorite solution (2.0 mL, Sd Fine Chem.) dropwise for about 10 min at RT and stirred for about another 1 h. The reaction mixture was diluted with DCM (30 mL) and washed with water (2×20 mL). The organic layer was dried over sodium sulphate and evaporated to dryness under reduced pressure. The resulting mixture was purified by silica gel chromatography eluting with 60 to 70% of EtOAc in hexane. Relevant fractions containing the target compound were combined and evaporated to dryness under reduced pressure to afford N-(4-fluoro-3-methoxybenzyl)-2-methyl-6-(5-(1-trityl-1H-imidazol-4-yl)-4,5-dihydroisoxazol-3-yl)pyrimidine-4-carboxamide as a light yellow solid 0.154 g, (37.5%). To a stirred solution of N-(4-fluoro-3-methoxybenzyl)-2-methyl-6-(5-(1-trityl-1H-imidazol-4-yl)-4,5-dihydroisoxazol-3-yl)pyrimidine-4-carboxamide(0.14 g, 0.24 mmol) in methanol (15 mL) was added concentrated HCl (1.2 mL). The reaction mixture was stirred at RT for about 4 h and excess solvent was evaporated under reduced pressure. The reaction mixture was quenched with 1N NaOH solution (5 mL), diluted with water (10 mL) and the product extracted with EtOAc (2×10 mL). The combined organic layers were washed successively with water (1×30 mL) and brine (1×20 mL). The organic layer was dried over sodium sulphate and evaporated to dryness under reduced pressure. The crude material was purified by preparative TLC (7% methanol in DCM) to afford 6-(5-(1H-imidazol-4-yl)-4,5-dihydroisoxazol-3-yl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide 0.039 g (41.4%); 1H NMR (400 MHz, DMSO): δ 8.178 (s, 1), 12.121 (s, 1H), 9.494 (m, 1H), 7.65 (s, 1H), 7.305 (s, 1H), 7.186-7.146 (m, 2H), 6.910-6.905 (m, 1H), 5.845-5.795 (m, 1H), 4.490-4.475 (d, 2H, J=6 Hz), 3.81 (s, 3H), 3.715-3.692 (m, 2H), 2.77 (s, 3H); MS m/z: 410.40 (M+H)+.

Workup

  1. washwashed with water (2×20 mL)
  2. dry with materialThe organic layer was dried over sodium sulphate
  3. customevaporated to dryness under reduced pressure
  4. customThe resulting mixture was purified by silica gel chromatography
  5. washeluting with 60 to 70% of EtOAc in hexane
  6. additionRelevant fractions containing the target compound
  7. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-ef199e4dbcbf4b94a6e925406644a135
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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