HCID 71143910, compound → HCID 86727266, compound

HRID 2173087Notes

Reaction equation

HRID 2173087 reaction equation
[C:1]([O:5][C:6]([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](Cl)[C:19]2[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=2[C:17]=1[F:34])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:35][N:36]1[C:40]([CH3:41])=[C:39]2[S:42][C:43]([Sn](CCCC)(CCCC)CCCC)=[CH:44][C:38]2=[N:37]1>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([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:43]2[S:42][C:39]3[C:38](=[N:37][N:36]([CH3:35])[C:40]=3[CH3:41])[CH:44]=2)[C:19]2[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=2[C:17]=1[F:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 71143910HCID 71143910, compoundHCID 86654740tert-Butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

Product 1

HCID 86727266HCID 86727266, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

In a 30 mL sealed cap glass tube, tert-butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (150 mg, 0.301 mmol), 2,3-dimethyl-5-(tributylstannyl)-2H-thieno[3,2-c]pyrazole (265 mg, 0.601 mmol) and tetrakis(triphenylphosphine)palladium(0) (174 mg, 0.150 mmol) were dissolved in toluene (5 mL). The cap was sealed and the reaction mixture was heated at 90° C. in an oil bath for 2 hours. The mixture was concentrated to give the intermediate, tert-butyl 6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)amino)-4-(2,3-dimethyl-2H-thieno[3,2-c]pyrazol-5-yl)-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate. The intermediate was dissolved in TFA (5 mL) and the reaction mixture was stirred for 90 minutes. The mixture was concentrated, dissolved in DMSO (5 mL), and purified via preparatory HPLC eluting with a gradient of 20-30% ACN (0.035% TFA) and H2O (0.05% TFA). The pure fractions were combined, evaporated to a minimal volume, and lyophilized to give a TFA salt of the title compound as a white solid (108 mg, 68.0%). 1H NMR (400 MHz, DMSO-d6) ppm 1.49-2.04 (m, 8H), 2.45 (s, 3H), 3.84 (br s, 1H), 3.92 (s, 3H), 4.27 (br s, 1H), 4.35-4.51 (m, 2H), 7.08 (d, J=6.06 Hz, 1H), 7.78 (br s, 3H), 8.60 (s, 1H), 9.25 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C20H23FN6OS, 415. found, 415.

Workup

  1. customIn a 30 mL sealed
  2. customcap glass tube
  3. customThe cap was sealed
  4. concentrationThe mixture was concentrated

Sources & evidence

ORD record
ord-f9130b4429b648c6b5a02ad0ece1821b
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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