Trifluoroacetic acid → 6-((1R,2S)-2-Aminocyclohexylamino)-4-(benzofuran-3-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 516037Notes

Reaction equation

HRID 516037 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([C:10]2[C:15]3[C:16](=[O:30])[N:17](CC4C=CC(OC)=CC=4OC)[CH2:18][C:14]=3[C:13]([F:31])=[C:12]([NH:32][C@@H:33]3[CH2:38][CH2:37][CH2:36][CH2:35][C@@H:34]3[NH:39]C(=O)OC(C)(C)C)[N:11]=2)=[CH:2]1.[C:47]([OH:53])([C:49]([F:52])([F:51])[F:50])=[O:48]>CS(C)=O.CCOC(C)=O.C1COCC1>[C:47]([OH:53])([C:49]([F:52])([F:51])[F:50])=[O:48].[NH2:39][C@H:34]1[CH2:35][CH2:36][CH2:37][CH2:38][C@H:33]1[NH:32][C:12]1[N:11]=[C:10]([C:3]2[C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[O:1][CH:2]=2)[C:15]2[C:16](=[O:30])[NH:17][CH2:18][C:14]=2[C:13]=1[F:31]

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86654720tert-Butyl (1S,2R)-2-(4-(benzofuran-3-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

Product 2

HCID 6422Trifluoroacetic acidHCID 532502146-((1R,2S)-2-Aminocyclohexylamino)-4-(benzofuran-3-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 20%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of tert-butyl (1S,2R)-2-(4-(benzofuran-3-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (75 mg, 0.119 mmol) and TFA (2 mL) was placed in a vial and heated at 125° C. for 3 h. The solvent was subsequently removed in vacuo to give a residue which was dispersed in DMSO and MeOH (1/1), passed through a microfiltration frit, and purified via preparative HPLC. The fractions were collected and the solvent removed in vacuo to give a TFA salt of the title compound as a gray solid (9.2 mg, 20%). 1H NMR (500 MHz, CD3OD) δ ppm 1.67 (br s, 3 H), 1.79-2.05 (m, 5 H), 3.98 (br s, 1 H), 4.50 (s, 2 H), 4.69 (br s, 1 H), 7.28-7.47 (m, 2 H), 7.56 (d, J=7.81 Hz, 1 H), 8.31 (d, J=6.83 Hz, 1 H), 9.08 (s, 1 H). [M+H] calc'd for C21H21FN4O2, 381; found, 381.

Workup

  1. customThe solvent was subsequently removed in vacuo
  2. customto give a residue which
  3. custompurified via preparative HPLC
  4. customThe fractions were collected
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-12f86498ec01461dae94d00c74b3e1ba
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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