Trifluoroacetic acid → 2-((1R,2S)-2-Aminocyclohexylamino)-4-(1-methyl-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one

HRID 515981Notes

Reaction equation

HRID 515981 reaction equation
COC1C=C(OC)C=CC=1C[N:6]1[C:14](=[O:15])[C:13]2[C:12]([C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)=[N:11][C:10]([NH:22][C@@H:23]3[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]3[NH:29]C(=O)OC(C)(C)C)=[N:9][C:8]=2[CH2:7]1.[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44]>>[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44].[NH2:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@H:23]1[NH:22][C:10]1[N:11]=[C:12]([C:16]2[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=2)[C:13]2[C:14](=[O:15])[NH:6][CH2:7][C:8]=2[N:9]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86654704tert-Butyl (1S,2R)-2-(6-(2,4-dimethoxybenzyl)-4-(1-methyl-1H-pyrazol-4-yl)-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamate

Product 2

HCID 6422Trifluoroacetic acidHCID 532519522-((1R,2S)-2-Aminocyclohexylamino)-4-(1-methyl-1H-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-oneYield 59%

Conditions

Temperature
70 °C

Procedure

tert-Butyl (1S,2R)-2-(6-(2,4-dimethoxybenzyl)-4-(1-methyl-1H-pyrazol-4-yl)-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamate (0.0625 g, 0.108 mmol) was dissolved in TFA (2 mL) and heated at 70° C. for 1 h. The solvent was removed under reduced pressure and the resulting residue was dispersed in DMSO/MeOH (1/1) solution. A pale purple precipitate was formed and was separated by filtration. The filtrate, which contained the product, was purified via reverse phase preparative HPLC. Lyophilized fractions gave a TFA salt of the title compound as a white solid (21 mg, 59%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.28-1.52 (m, 2 H) 1.51-1.94 (m, 6 H) 3.93 (s, 3 H) 4.14-4.30 (m, 2 H) 4.29-4.58 (m, 1 H) 7.51 (d, J=6.83 Hz, 1 H) 7.71 (br s, 2 H) 8.29 (s, 1 H) 8.34-8.69 (m, 1 H) 9.11 (d, J=17.09 Hz, 1 H). [M+H] calc'd for C16H21N7O, 328; found, 328.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe resulting residue was dispersed in DMSO/MeOH (1/1) solution
  3. customA pale purple precipitate was formed
  4. customwas separated by filtration
  5. customwas purified via reverse phase preparative HPLC

Sources & evidence

ORD record
ord-5ab8ec431a0b49b8a7c54569e4202b8b
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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