Trifluoroacetic acid → Trifluoroacetic acid

HRID 516111Notes

Reaction equation

HRID 516111 reaction equation
C(OC([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([C:22]2[S:26][C:25]([NH:27]C(=O)OC(C)(C)C)=[N:24][CH:23]=2)[C:19]2[C:35](=[O:49])[N:36](CC3C=CC(OC)=CC=3OC)[CH2:37][C:18]=2[C:17]=1[F:50])=O)(C)(C)C.[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52]>>[NH2:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([C:22]2[S:26][C:25]([NH2:27])=[N:24][CH:23]=2)[C:19]2[C:35](=[O:49])[NH:36][CH2:37][C:18]=2[C:17]=1[F:50].[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86654741tert-Butyl (5-(6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)amino)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)-1,3-thiazol-2-yl)carbamate

Product 2

HCID 6422Trifluoroacetic acidYield 32%HCID 866547426-((1R,2S)-2-Aminocyclohexylamino)-4-(2-aminothiazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Procedure

A solution of tert-butyl (5-(6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclo-hexyl)amino)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)-1,3-thiazol-2-yl)carbamate (41.5 mg, 0.058 mmol) in TFA (5 mL) was heated to 65° C. for 3 h. After removal of the solvent, the resulting crude material was reconstituted in MeOH/DMF (6.0 mL) and purified via preparative HPLC eluting with water (0.05% TFA) and ACN (10-20% gradient, 0.035% TFA). The collected fractions were stripped to dryness via rotary evaporation to yield the title compound as a TFA salt (6.7 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-2.11 (m, 9 H), 3.73 (br s, 2 H), 4.19 (d, J=3.79 Hz, 1 H), 4.41 (d, J=3.03 Hz, 2 H), 6.95 (d, J=3.03 Hz, 1 H), 7.77 (br s, 2 H), 8.44 (s, 1 H), 8.93 (s, 1 H). [M+H] calc'd for C16H19FN6OS, 363; found, 363.

Workup

  1. customAfter removal of the solvent
  2. custompurified via preparative HPLC
  3. washeluting with water (0.05% TFA) and ACN (10-20% gradient, 0.035% TFA)
  4. customThe collected fractions were stripped to dryness via rotary evaporation

Sources & evidence

ORD record
ord-420517c5fd0c45e6b1120183f51b7a4a
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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