HCID 10740978, compound → HCID 71143930, compound

HRID 2173073Notes

Reaction equation

HRID 2173073 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20](Cl)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Sn](CCCC)(CCCC)[C:40]1[S:48][C:43]2=[CH:44][N:45]=[CH:46][CH:47]=[C:42]2[CH:41]=1)CCC>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(O)=O.[Na+].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:40]3[S:48][C:43]4=[CH:44][N:45]=[CH:46][CH:47]=[C:42]4[CH:41]=3)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 2

HCID 10740978HCID 10740978, compoundHCID 86654748tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

Product 1

HCID 71143930HCID 71143930, compound

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (53 mg, 0.106 mmol), 2-(tributylstannyl)thieno[2,3-c]pyridine (44.9 mg, 0.106 mmol) and tetrakis(triphenylphosphine) palladium(0) (122 mg, 0.106 mmol) in toluene (3 mL) was heated to 120° C. in a microwave for 60 minutes. The reaction mixture was diluted with EtOAc (50 mL) and saturated aqueous NaHCO3 (100 mL). The organic layer was separated and the aqueous layer was washed with EtOAc (50 mL). The organic layers were combined and dried over Na2SO4, and the solvent was removed in vacuo to give the intermediate, tert-butyl 6-(((3R,4R)-3-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-yl)amino)-7-fluoro-3-oxo-4-(thieno[2,3-c]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate. The intermediate was dispersed in TFA and DCM (10 mL). The mixture was stirred at room temperature for 60 minutes and then concentrated. The resulting crude material was reconstituted in MeOH and DCM (10.0 mL) and purified via preparative HPLC, eluting with a gradient of 10-25% ACN (0.035% TFA) and H2O (0.05% TFA). The collected fractions were combined and diluted with EtOAc (50 mL) and saturated aqueous NaHCO3 (100 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (50 mL). The organic layers were combined and dried over Na2SO4, and the solvent was removed in vacuo to give the title compound (5.8 mg, 14%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.83 (d, J=8.79 Hz, 1H), 2.10-2.27 (m, 1H), 3.81-3.92 (m, 2H), 3.98-4.16 (m, 3H), 4.34-4.48 (m, 1H), 4.52 (br s, 2H), 7.55 (d, J=5.37 Hz, 1H), 7.97-8.08 (m, 3H), 8.53 (br s, 1H), 8.75 (s, 1H), 9.34 (br s, 1H), 9.53 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C19H18FN5O2S, 400. found, 400.

Workup

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed with EtOAc (50 mL)
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-a3f7e94d8c3343e595ceed1b20eb6cd1
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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