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 → 2-((1R,2S)-2-Aminocyclohexylamino)-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one

HRID 515955Notes

Reaction equation

HRID 515955 reaction equation
COC1C=C(OC)C=CC=1C[N:6]1[C:14](=[O:15])[C:13]2[C:12]([NH:16][C:17]3[CH:18]=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=3)=[N:11][C:10]([NH:24][C@@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]3[NH:31]C(=O)OC(C)(C)C)=[N:9][C:8]=2[CH2:7]1>C(O)(C(F)(F)F)=O>[NH2:31][C@H:26]1[CH2:27][CH2:28][CH2:29][CH2:30][C@H:25]1[NH:24][C:10]1[N:11]=[C:12]([NH:16][C:17]2[CH:18]=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=2)[C:13]2[C:14](=[O:15])[NH:6][CH2:7][C:8]=2[N:9]=1

Participants

3

Reactant 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)cyclohexylcarbamate

Product 1

HCID 532517972-((1R,2S)-2-Aminocyclohexylamino)-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-oneYield 44%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of crude 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 (235 mg, 0.390 mmol) in TFA (5 mL) was stirred at 60° C. for 2 h and was then purified by reverse phase preparative HPLC. The fractions were collected, concentrated under reduced pressure, diluted in EtOAc, and basified with an aqueous saturated solution of NaHCO3. The organic extract was dried and concentrated under reduced pressure to give the title compound as a white solid (60 mg, 44%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33-1.60 (m, 10 H), 2.32 (s, 3 H), 3.16 (m, 2 H), 3.92 (br s, 1 H), 4.14 (s, 2 H), 6.88 (d, J=7.07 Hz, 1 H), 7.13 (br s, 1 H), 7.22 (t, J=7.45 Hz, 1 H), 7.34-7.55 (m, 1 H), 7.70 (br s, 1 H), 8.01 (br s, 1 H), 8.58 (br s, 1 H). [M+H] calc'd for C19H24N6O, 353; found, 353.

Workup

  1. customwas then purified by reverse phase preparative HPLC
  2. customThe fractions were collected
  3. concentrationconcentrated under reduced pressure
  4. additiondiluted in EtOAc
  5. extractionThe organic extract
  6. customwas dried
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d2326f9343dd4cb7bd6905356ed4c20d
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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