Water → HCID 86680659, compound

HRID 1615420Notes

Reaction equation

HRID 1615420 reaction equation
[CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=1)(=[O:6])=[O:5])([CH3:3])[CH3:2].[C:16]([O:20][C:21]([N:23]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[C:24]1[C:25]([C:31]2[O:35][N:34]=[C:33]([C:36]3[CH:41]=[CH:40][C:39]([C@@H:42]4[CH2:47][O:46][CH2:45][CH2:44][N:43]4[C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[CH:38][CH:37]=3)[CH:32]=2)=[N:26][C:27](Br)=[CH:28][N:29]=1)=[O:22])([CH3:19])([CH3:18])[CH3:17].C([O-])([O-])=O.[Na+].[Na+].O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.CC#N>[C:58]([O:57][C:55]([N:23]([C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[C:24]1[C:25]([C:31]2[O:35][N:34]=[C:33]([C:36]3[CH:41]=[CH:40][C:39]([C@@H:42]4[CH2:47][O:46][CH2:45][CH2:44][N:43]4[C:48]([O:50][C:51]([CH3:53])([CH3:52])[CH3:54])=[O:49])=[CH:38][CH:37]=3)[CH:32]=2)=[N:26][C:27]([C:10]2[CH:11]=[CH:12][C:7]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:6])=[O:5])=[CH:8][CH:9]=2)=[CH:28][N:29]=1)=[O:56])([CH3:61])([CH3:59])[CH3:60]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 441193274-(Isopropylsulphonyl)benzeneboronic acidHCID 86680660HCID 86680660, compound

Product 1

HCID 86680659HCID 86680659, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (4-isopropylsulfonylphenyl)boronic acid (892.7 mg, 3.914 mmol), tert-butyl (3R)-3-[4-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazin-2-yl]isoxazol-3-yl]phenyl]morpholine-4-carboxylate (2.5 g, 3.558 mmol), Na2CO3 (3.558 mL of 2 M, 7.116 mmol), water (17.60 mL) and MeCN (25.00 mL) were degassed by vacuum/nitrogen cycles (3×) then Pd[P(tBu)3]2 (90.92 mg, 0.1779 mmol) was added and vessel flushed with nitrogen via vacuum/nitrogen cycles (2×). Mixture then heated at 50° C. (drysyn block temp) for 3 h. The reaction was cooled to rt, and then diluted with EtOAc (10 mL) and water (10 mL) and the organic layer separated and then washed with water (2×10 mL) and brine (1×10 mL), dried MgSO4, filtered and concentrated in vacuo. The crude product purified by ISCO (120 g SiO2, 0 to 50% EtOAc/petroleum ether) to leave product as a white foam (2.52 g, 88% yield)

Workup

  1. customwere degassed by vacuum/nitrogen cycles (3×)
  2. customvessel flushed with nitrogen via vacuum/nitrogen cycles (2×)
  3. temperatureThe reaction was cooled to rt
  4. additiondiluted with EtOAc (10 mL) and water (10 mL)
  5. customthe organic layer separated
  6. washwashed with water (2×10 mL) and brine (1×10 mL), dried MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product purified by ISCO (120 g SiO2, 0 to 50% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-93fb027b28ea48c88a8e7064ddc59a06
Source dataset
uspto-grants-2014_07
Patent number
US08765751B2

Reaction notes

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