Water → HCID 86682778, compound

HRID 78721Notes

Reaction equation

HRID 78721 reaction equation
[C:1]([O:5][C:6](=[O:33])[N:7]([C:15]1[C:20]([C:21]2[O:22][C:23]([C:26]3[S:27][CH:28]=[CH:29][C:30]=3[CH3:31])=[N:24][N:25]=2)=[N:19][C:18](Br)=[CH:17][N:16]=1)C(OC(C)(C)C)=O)([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:42]2[CH:47]=[CH:46][C:45]([S:48]([CH:51]3[CH2:56][CH2:55][CH2:54][N:53]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:52]3)(=[O:50])=[O:49])=[CH:44][CH:43]=2)O1.O.C([O-])([O-])=O.[Na+].[Na+]>CC#N>[C:1]([O:5][C:6]([NH:7][C:15]1[N:16]=[CH:17][C:18]([C:42]2[CH:47]=[CH:46][C:45]([S:48]([CH:51]3[CH2:56][CH2:55][CH2:54][N:53]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:52]3)(=[O:50])=[O:49])=[CH:44][CH:43]=2)=[N:19][C:20]=1[C:21]1[O:22][C:23]([C:26]2[S:27][CH:28]=[CH:29][C:30]=2[CH3:31])=[N:24][N:25]=1)=[O:33])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 59472351HCID 59472351, compoundHCID 86682773Tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate

Product 1

HCID 86682778HCID 86682778, compoundYield 106.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

tert-butyl-N-[5-bromo-3-[5-(3-methyl-2-thienyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (750 mg, 1.393 mmol) and tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (691.5 mg, 1.532 mmol) were suspended in MeCN (7.500 mL)/water (7.500 mL) and Na2CO3 (1.393 mL of 2 M, 2.786 mmol) was added. The reaction mixture was degassed with 3× nitrogen/vacuum cycles. Pd(tBu3P)2 (71.19 mg, 0.1393 mmol) was added and the reaction mixture again degassed 3 times then heated to 65° C. (Dry Syn Temp) for 1.5 hours. The reaction mixture was cooled to ambient temperature and diluted with ethylacetate/water. The aqueous layer was extracted with ethylacetate (×1) and the combined organic extracts washed with brine (×2), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 80 g column, eluting with 0 to 30% ethyl acetate/petroleum Ether, (loaded in DCM) to give the sub-title product as a yellow solid (1.01 g, 93% Yield). H NMR (400.0 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.59 (d, 2H), 8.16 (d, 2H), 7.96 (d, 1H), 7.24 (d, 1H), 4.14-3.92 (m, 1H), 3.77 (br d, 1H), 3.44 (br s, 1H), 3.02-2.91 (m, 1H), 2.79 (br t, 1H), 2.67 (s, 3H), 2.05 (br s, 1H), 1.76-1.58 (m, 2H) and 1.35-1.22 (m, 28H) ppm; LC/MS m/z 627 [M−100−56]+.

Workup

  1. additionwas added
  2. customThe reaction mixture was degassed with 3× nitrogen/vacuum cycles
  3. customthe reaction mixture again degassed 3 times
  4. custom(Dry Syn Temp) for 1.5 hours
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. additiondiluted with ethylacetate/water
  7. extractionThe aqueous layer was extracted with ethylacetate (×1)
  8. washthe combined organic extracts washed with brine (×2)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by column chromatography (ISCO Companion, 80 g column
  13. washeluting with 0 to 30% ethyl acetate/petroleum Ether, (loaded in DCM)

Sources & evidence

ORD record
ord-951118c0781444d9aec6b0c7f7a0aa3c
Source dataset
uspto-grants-2014_09
Patent number
US08841449B2

Reaction notes

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