Sodium Carbonate → HCID 89908297, compound

HRID 923835Notes

Reaction equation

HRID 923835 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[N:22]1[CH2:26][C@H:25]([OH:27])[C@@H:24]([OH:28])[CH2:23]1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].[N:29]1[CH:34]=[C:33](B(O)O)[CH:32]=[N:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:28][C@@H:24]1[C@@H:25]([OH:27])[CH2:26][N:22]([C:21]2[CH:20]=[CH:19][C:4]([C:5]([NH:7][C:8]3[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=3)=[O:6])=[CH:3][C:2]=2[C:33]2[CH:34]=[N:29][CH:30]=[N:31][CH:32]=2)[CH2:23]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 899064793-Bromo-4-((3 S,4S)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Product 1

HCID 89908297HCID 89908297, compound

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

3-Bromo-4-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 7.1, 60 mg, 0.13 mmol), pyrimidin-5-ylboronic acid (66.6 mg, 0.325 mmol), Pd(PPh3)2Cl2 (9.13 mg, 0.013 mmol) and Na2CO3 (68.9 mg, 0.650 mmol) were added to a MW vial. The vial was sealed, evacuated/purged with argon, and DME (552 μL), water (158 μL), EtOH (79 μL) were added. The RM was then subjected to MW irradiation at 120° C. for 10 min. The RM was diluted with DME (2 mL), treated with Si-Thiol (Silicycle, 1.27 mmol/g, 102 mg, 0.130 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 12, from 20% to 50% in 18 min) to yield the title compound as a white solid. UPLC-MS (condition 1) tR=2.10 min, m/z=461.0 [M+H]+, m/z=459.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.75 (d, J=10.27 Hz, 2H) 3.27 (dd, J=10.39, 3.55 Hz, 2H) 3.88 (br. s, 2H) 5.07 (d, J=3.42 Hz, 2H) 6.97 (d, J=8.80 Hz, 1H) 7.34 (d, J=8.31 Hz, 2H) 7.82-7.90 (m, 3H) 7.94 (dd, J=8.80, 2.45 Hz, 1H) 8.85 (s, 2H) 9.17 (s, 1H) 10.10 (s, 1H).

Workup

  1. customThe vial was sealed
  2. customevacuated/purged with argon, and DME (552 μL), water (158 μL), EtOH (79 μL)
  3. additionwere added
  4. customThe RM was then subjected to MW irradiation at 120° C. for 10 min
  5. additionThe RM was diluted with DME (2 mL)
  6. filtrationfiltered
  7. customthe filtrate was evaporated off under reduced pressure
  8. customto give a residue which
  9. customwas purified by preparative HPLC (Condition 12, from 20% to 50% in 18 min)

Sources & evidence

ORD record
ord-5c674556c26b4a2d853ee62dd34fc028
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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