Hydrazine hydrate (1:1) → tert-Butyl (1S,2R)-2-(5-oxo-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamate

HRID 711427Notes

Reaction equation

HRID 711427 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]([CH2:22][N:23]2[C:31](=[O:32])C3C(=CC=CC=3)C2=O)[C:19](C(OCC)=O)=[C:18]([NH:39][C:40]2[CH:41]=[C:42]([CH3:46])[CH:43]=[CH:44][CH:45]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.NN>CCO>[O:32]=[C:31]1[C:19]2[C:18]([NH:39][C:40]3[CH:41]=[C:42]([CH3:46])[CH:43]=[CH:44][CH:45]=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]([CH3:2])([CH3:3])[CH3:4])=[N:21][C:20]=2[CH2:22][NH:23]1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58317681Ethyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate

Product 1

HCID 86654703tert-Butyl (1S,2R)-2-(5-oxo-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamateYield 44.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of ethyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate (109 mg, 0.174 mmol) and hydrazine hydrate (36.5 mg, 0.729 mmol) in EtOH (2 mL) was stirred at 65° C. for 12 h. After cooling, the mixture was concentrated under reduced pressure and the residue was treated with water and extracted with EtOAc. The combined organic layers were washed with aqueous NaHCO3, water, and brine, were filtered through SiO2, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from EtOAc/hexanes and filtered to give the title compound (34.8 mg). The filtrate was concentrated and triturated with IPE to give a second batch (20.3 mg) of the title compound (total 65.1 mg, 83%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.24-1.79 (m, 17H), 2.32 (s, 3H), 3.84 (br s, 1H), 4.06 (br s, 1H), 4.14 (s, 2H), 6.55-6.70 (m, 1H), 6.87-7.04 (m, 2H), 7.20-7.24 (m, 1H), 7.40-7.48 (m, 1H), 7.68-7.80 (m, 1H), 8.01-8.06 (m, 1H), 8.56-8.59 (m, 1H). [M+H] calc'd for C24H33N6O3, 453. found, 453.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated under reduced pressure
  3. additionthe residue was treated with water
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with aqueous NaHCO3, water, and brine
  6. filtrationwere filtered through SiO2
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was recrystallized from EtOAc/hexanes
  9. filtrationfiltered

Sources & evidence

ORD record
ord-8469d3b183c448819d30b5167a116b45
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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