(5-Fluoro-1-benzothiophen-2-yl)boronic acid → HCID 71143874, compound

HRID 2173071Notes

Reaction equation

HRID 2173071 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].[F:35][C:36]1[CH:47]=[CH:46][C:39]2[S:40][C:41](B(O)O)=[CH:42][C:38]=2[CH:37]=1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(O)=O.[Na+].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[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:41]3[S:40][C:39]4[CH:46]=[CH:47][C:36]([F:35])=[CH:37][C:38]=4[CH:42]=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 53234193(5-Fluoro-1-benzothiophen-2-yl)boronic acidHCID 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 71143874HCID 71143874, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 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 (33 mg, 0.066 mmol), 5-fluorobenzo[b]thiophen-2-ylboronic acid (12.91 mg, 0.066 mmol) and tetrakis(triphenylphosphine)palladium(0) (76 mg, 0.066 mmol) in toluene (3 mL) was heated to 120° C. via microwave irradiation for 30 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-4-(5-fluorobenzo[b]thiophen-2-yl)-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate. The intermediate was dispersed in TFA and DCM (1:1, 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 (6.0 mL) and purified via preparative HPLC, eluting with a gradient of 25-30% ACN (0.035% TFA) and H2O (0.05% TFA). The collected fractions were combined and the solvent was stripped to dryness via rotary evaporation to yield a TFA salt of the title compound (12 mg, 44%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.82 (d, J=9.76 Hz, 1H), 2.15 (d, J=8.30 Hz, 1H), 3.59-3.70 (m, 1H), 3.82 (s, 1H), 3.91 (br s, 1H), 3.98-4.11 (m, 2H), 4.38 (br s, 1H), 4.43-4.55 (m, 2H), 7.23-7.33 (m, 1H), 7.42 (d, J=4.88 Hz, 1H), 7.76 (dd, J=9.76, 2.44 Hz, 1H), 7.93-8.03 (m, 3H), 8.62-8.74 (m, 1H), 9.41 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C20H18F2N4O2S, 417. found, 417.

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-cd07a65cf8a24f3f9af2703b6ea63ccd
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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