(R)-2-(4-(5-Cyanothiophen-2-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamide → (R)-2-(4-(5-Cyanothiophen-2-yl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamide

HRID 516115

Reaction equation

HRID 516115 reaction equation
[C:1]([C:3]1[S:7][C:6]([C:8]2[C:13]3[C:14](=[O:28])[N:15](CC4C=CC(OC)=CC=4OC)[CH2:16][C:12]=3[C:11]([F:29])=[C:10]([NH:30][C@H:31]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:32]([NH2:34])=[O:33])[N:9]=2)=[CH:5][CH:4]=1)#[N:2]>C(O)(C(F)(F)F)=O>[C:1]([C:3]1[S:7][C:6]([C:8]2[C:13]3[C:14](=[O:28])[NH:15][CH2:16][C:12]=3[C:11]([F:29])=[C:10]([NH:30][C@H:31]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:32]([NH2:34])=[O:33])[N:9]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

3

Reactant 1

HCID 58317612(R)-2-(4-(5-Cyanothiophen-2-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamide

Product 1

HCID 58317635(R)-2-(4-(5-Cyanothiophen-2-yl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamideYield 17%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (R)-2-(4-(5-cyanothiophen-2-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamide (68 mg, 0.126 mmol) in TFA (2 mL) was heated to 65° C. for 3 h. After removal of the solvent, the resulting crude material was reconstituted in MeOH/DCM (3.0 mL) and purified via preparative HPLC eluting with water (0.05% TFA) and ACN (40%, 0.035% TFA). The collected fractions were combined and the solvent was removed via rotary evaporation to yield the title compound (8.3 mg, 17%). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.86-0.96 (m, 6 H), 1.53-1.62 (m, 1 H), 1.67-1.88 (m, 2 H), 4.45 (s, 2 H), 4.50-4.57 (m, 1 H), 6.96-7.06 (m, 1 H), 7.32-7.54 (m, 2 H), 7.86-8.02 (m, 1 H), 8.61 (s, 1 H), 9.00-9.15 (m, 1 H). [M+H] calc'd for C18H18FN5O2S, 388; found, 388.

Workup

  1. customAfter removal of the solvent
  2. custompurified via preparative HPLC
  3. washeluting with water (0.05% TFA) and ACN (40%, 0.035% TFA)
  4. customthe solvent was removed via rotary evaporation

Sources & evidence

ORD record
ord-85b9285064684067aba863034c3bf57e
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Linked notes

Loading…