Dimethyl Sulfoxide → N-((1R,4R)-4-(tert-butyldiphenylsilyloxy)-7-fluoro-1,2,3,4-tetrahydronaphthalen-1-yl)-2-(6-fluoro-1H-benzo[d]imidazol-1-yl)-5-nitropyrimidin-4-amine

HRID 1363245Notes

Reaction equation

HRID 1363245 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[N:15]=[C:14](SC#N)[C:13]([N+:19]([O-:21])=[O:20])=[CH:12][N:11]=3)[C:6]=2[CH:22]=1.[Si:23]([O:40][C@H:41]1[C:50]2[C:45](=[CH:46][C:47]([F:51])=[CH:48][CH:49]=2)[C@H:44]([NH2:52])[CH2:43][CH2:42]1)([C:36]([CH3:39])([CH3:38])[CH3:37])([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CCN(C(C)C)C(C)C.CS(C)=O>C1COCC1>[Si:23]([O:40][C@H:41]1[C:50]2[C:45](=[CH:46][C:47]([F:51])=[CH:48][CH:49]=2)[C@H:44]([NH:52][C:14]2[C:13]([N+:19]([O-:21])=[O:20])=[CH:12][N:11]=[C:10]([N:7]3[C:6]4[CH:22]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[N:9]=[CH:8]3)[N:15]=2)[CH2:43][CH2:42]1)([C:36]([CH3:39])([CH3:37])[CH3:38])([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 597049556-Fluoro-1-(5-nitro-4-thiocyanatopyrimidin-2-yl)-1H-benzo[d]imidazoleHCID 59846380(1R,4R)-4-(tert-butyldiphenylsilyloxy)-7-fluoro-1,2,3,4-tetrahydronaphthalen-1-amine

Product 1

HCID 59846358N-((1R,4R)-4-(tert-butyldiphenylsilyloxy)-7-fluoro-1,2,3,4-tetrahydronaphthalen-1-yl)-2-(6-fluoro-1H-benzo[d]imidazol-1-yl)-5-nitropyrimidin-4-amineYield 65.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-Fluoro-1-(5-nitro-4-thiocyanatopyrimidin-2-yl)-1H-benzo[d]imidazole (498 mg, 1.57 mmol, 1.1 equiv) was added to a solution of (1R,4R)-4-(tert-butyldiphenylsilyloxy)-7-fluoro-1,2,3,4-tetrahydronaphthalen-1-amine (600 mg, 1.43 mmol, 1 equiv) in THF (20 mL) containing DIEA (1.5 mL), followed by adding 2 mL of DMSO. The resulted red solution was stirred at RT for 16 h. THF was evaporated off The residue was dissolved in EtOAc, washed with water and brine, dried (Na2SO4). The organic layer was evaporated to dryness. The residue was purified on ISCO (12 g column, MeOH—CH2Cl2 0-5%) to give a yellow solid product (633 mg, 65%). MS (ESI): 677.3.

Workup

  1. customTHF was evaporated off The residue
  2. dissolutionwas dissolved in EtOAc
  3. washwashed with water and brine
  4. dry with materialdried (Na2SO4)
  5. customThe organic layer was evaporated to dryness
  6. customThe residue was purified on ISCO (12 g column, MeOH—CH2Cl2 0-5%)

Sources & evidence

ORD record
ord-243f50c619b3441baa35016ac8c21433
Source dataset
uspto-grants-2011_02
Patent number
US07884109B2

Reaction notes

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