Trifluoroacetic acid → Trifluoroacetic acid

HRID 2092884Notes

Reaction equation

HRID 2092884 reaction equation
COC1C=C(OC)C=CC=1C[N:6]1[CH2:14][C:13]2[C:12]([F:15])=[C:11]([NH:16][C@@H:17]3[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]3[NH:23]C(=O)OC(C)(C)C)[N:10]=[C:9]([C:31]3[S:32][C:33]([CH3:36])=[CH:34][CH:35]=3)[C:8]=2[C:7]1=[O:37].[C:44]([OH:50])([C:46]([F:49])([F:48])[F:47])=[O:45]>>[NH2:23][C@@H:18]1[C@H:17]([NH:16][C:11]2[N:10]=[C:9]([C:31]3[S:32][C:33]([CH3:36])=[CH:34][CH:35]=3)[C:8]3[C:7](=[O:37])[NH:6][CH2:14][C:13]=3[C:12]=2[F:15])[CH2:22][CH2:21][O:20][CH2:19]1.[C:44]([OH:50])([C:46]([F:49])([F:48])[F:47])=[O:45]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86654747tert-Butyl (3R,4R)-4-(2-(2,4-dimethoxybenzyl)-7-fluoro-4-(5-methylthiophen-2-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)tetrahydro-2H-pyran-3-ylcarbamate

Product 2

HCID 6422Trifluoroacetic acidYield 74%HCID 532510096-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(5-methylthiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Procedure

A solution of tert-butyl (3R,4R)-4-(2-(2,4-dimethoxybenzyl)-7-fluoro-4-(5-methylthiophen-2-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (31 mg, 0.051 mmol) in TFA (10 mL) was heated to 80° C. for 1 h. After the solvent was removed, the residue was dissolved in MeOH and DCM (8 mL) and was purified via preparative HPLC eluting with water (0.05% TFA) and ACN (15-30% gradient, 0.035% TFA). The collected fractions were combined and the solvent was stripped to dryness via rotary evaporation to give the title compound as a TFA salt (13.5 mg, 74%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.78 (d, J=13.18 Hz, 1H), 2.03-2.18 (m, 1H), 2.46 (s, 3H), 3.17 (d, J=4.88 Hz, 1H), 3.55-3.65 (m, 1H), 3.75 (d, J=13.18 Hz, 1H), 3.85 (br s, 1H), 3.96-4.06 (m, 2H), 4.41 (d, J=7.81 Hz, 2H), 6.84 (d, J=2.44 Hz, 1H), 7.22 (d, J=4.88 Hz, 1H), 7.92 (br s, 2H), 8.47 (s, 1H), 8.83 (d, J=3.42 Hz, 1H). [M+H] calc'd for C17H19FN4O2S, 363. found, 363.

Workup

  1. customAfter the solvent was removed
  2. dissolutionthe residue was dissolved in MeOH
  3. customDCM (8 mL) and was purified via preparative HPLC
  4. washeluting with water (0.05% TFA) and ACN (15-30% gradient, 0.035% TFA)
  5. customthe solvent was stripped to dryness via rotary evaporation

Sources & evidence

ORD record
ord-79e5a9b376994922b528b3644e847fcc
Source dataset
uspto-grants-2013_05
Patent number
US08440689B2

Reaction notes

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