Trifluoroacetic acid → 6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 516092Notes

Reaction equation

[NH2:1][C@@H:2]1[C@H:7]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[CH:16]=[N:17][N:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=34)[C:12]3[C:24](=[O:38])[N:25](CC4C=CC(OC)=CC=4OC)[CH2:26][C:11]=3[C:10]=2[F:39])[CH2:6][CH2:5][O:4][CH2:3]1.[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]>>[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41].[NH2:1][C@@H:2]1[C@H:7]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[CH:16]=[N:17][N:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=34)[C:12]3[C:24](=[O:38])[NH:25][CH2:26][C:11]=3[C:10]=2[F:39])[CH2:6][CH2:5][O:4][CH2:3]1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 672382796-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-2-(2,4-dimethoxybenzyl)-7-fluoro-4-(pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Product 2

HCID 6422Trifluoroacetic acid

HCID 583175466-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 44.2%

Conditions

Temperature: 60 °C

Procedure

To a 25 mL round bottom flask with a stir bar was added 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-2-(2,4-dimethoxybenzyl)-7-fluoro-4-(pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (85 mg, 0.160 mmol) in TFA (5 mL). The mixture was heated at 60° C. for 1.5 h and then cooled to RT. The mixture was concentrated and purified via preparative HPLC to give a TFA salt of the title compound as a white solid (27 mg, 44.2%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.83-1.85 (m, 1 H), 2.12-2.14 (m, 1 H), 3.65-3.73 (m, 2 H), 3.81-3.82 (m, 1 H), 3.93-3.95 (m, 1 H), 4.01-4.03 (m, 1 H), 4.43 (s, 2 H), 4.53-4.55 (m, 1 H), 7.04 (t, J=6.83 Hz, 1 H), 7.13 (d, J=4.88 Hz, 1 H), 7.49 (t, J=8.05 Hz, 1 H), 7.94 (br s, 1 H), 8.36-8.42 (m, 2 H), 8.78 (d, J=6.83 Hz, 1 H), 9.33 (s, 1 H). [M+H] calc'd for C19H19FN6O2, 383; found, 383.

Workup

temperaturecooled to RT
concentrationThe mixture was concentrated
custompurified via preparative HPLC

Sources & evidence

ORD record: ord-9cfb0fc9232a45fd86147725cd460613
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108970B2

Reaction notes

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