Selenium Dioxide → tert-butyl (1S,2R)-2-(6-(2,4-dimethoxybenzyl)-5-oxo-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamate

HRID 711421Notes

Reaction equation

HRID 711421 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([CH3:22])[C:19]([C:23](OC)=[O:24])=[C:18]([NH:27][C:28]2[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Se](=O)=O.[CH3:38][O:39][C:40]1[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[CH:42][C:41]=1[CH2:48][NH2:49].C([BH3-])#N.[Na+]>O1CCOCC1.CO>[CH3:38][O:39][C:40]1[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[CH:42][C:41]=1[CH2:48][N:49]1[C:23](=[O:24])[C:19]2[C:18]([NH:27][C:28]3[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=3)=[N:17][C:16]([NH:15][C@@H:10]3[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[N:21][C:20]=2[CH2:22]1

Participants

7

Reactant 4

HCID 24007Selenium DioxideHCID 5972502,4-DimethoxybenzylamineHCID 5003444Sodium cyanoborohydrideHCID 67238015Methyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-methyl-6-(m-tolylamino)pyrimidine-5-carboxylate

Product 1

HCID 86654702tert-butyl (1S,2R)-2-(6-(2,4-dimethoxybenzyl)-5-oxo-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamateYield 37%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-methyl-6-(m-tolylamino)pyrimidine-5-carboxylate (500 mg, 1.065 mmol) and selenium dioxide (236 mg, 2.130 mmol) in dioxane (10 mL) was heated at 100° C. for 24 h. The solution was subsequently cooled and filtered. The filtrate was concentrated under reduced pressure and dried to give a brown foam (534 mg; dihydroxyl form was observed via mass spectroscopy), which was used directly in the next step without further purification. A mixture of the unpurified intermediate (534 mg, 1.065 mmol) and (2,4-dimethoxyphenyl)methanamine (0.160 mL, 1.065 mmol) in MeOH (10 mL) was stirred at RT for 10 min, after which sodium cyanoborohydride (100 mg, 1.597 mmol) was added, and the reaction mixture was stirred at RT for 20 h. The reaction mixture was warmed to 50° C. and stirred for an additional 2 h to complete the reaction. The mixture was cooled to RT and the solid filtered and washed with MeOH to give the title compound as a pinkish solid (237 mg, 37%). [M+H] calc'd for C33H42N6O5, 603. found, 603.

Workup

  1. temperatureThe solution was subsequently cooled
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customdried
  5. customto give a brown foam (534 mg; dihydroxyl form was observed via mass spectroscopy), which
  6. customwas used directly in the next step without further purification
  7. stirringthe reaction mixture was stirred at RT for 20 h
  8. temperatureThe reaction mixture was warmed to 50° C.
  9. stirringstirred for an additional 2 h
  10. customthe reaction
  11. temperatureThe mixture was cooled to RT
  12. filtrationthe solid filtered
  13. washwashed with MeOH

Sources & evidence

ORD record
ord-803a773fc4294270b2fbc7a19de2da35
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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