Sodium Carbonate → HCID 118195369, compound

HRID 923909Notes

Reaction equation

HRID 923909 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[F:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[N:34][CH:35]=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>[F:29][C:30]1[CH:31]=[C:32]([C:2]2[C:3]([N:22]3[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[CH2:23]3)=[N:4][CH:5]=[C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:18])[F:19])=[CH:12][CH:11]=3)=[O:8])[CH:21]=2)[CH:33]=[N:34][CH:35]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 44717403(5-Fluoropyridin-3-yl)boronic acidHCID 86702601(S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 118195369HCID 118195369, compound

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

(S)-5-Bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 78.1, 60 mg, 0.13 mmol), (5-fluoropyridin-3-yl)boronic acid (60.8 mg, 0.261 mmol), Pd(PPh3)2Cl2 (9.15 mg, 0.013 mmol) and Na2CO3 (41.5 mg, 0.391 mmol) were added to a MW vial. The vial was sealed, evacuated/purged with argon, and DME (553 μL), water (158 μL) and EtOH (79 μL) were added. The RM was subjected to MW irradiation at 120° C. for 15 min. The RM was diluted with DME (2 mL), treated with Si-Thiol (Silicycle, 1.27 mmol/g, 103 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, 15% to 45% in 14 min) to yield the title compound as a yellow solid. UPLC-MS (condition 1) tR=1.90 min, m/z=487.0 [M+H]+, m/z=485.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.27 (t, J=7.58 Hz, 3H) 1.50-1.62 (m, 1H) 1.77-1.89 (m, 1H) 2.15-2.28 (m, 1H) 2.82 (q, J=7.58 Hz, 2H) 2.99 (dd, J=11.00, 6.60 Hz, 1H) 3.08-3.20 (m, 2H) 3.21-3.30 (m, 2H) 3.29-3.38 (m, 1H) 4.60 (br. s, 1H) 7.34 (d, J=8.80 Hz, 2H) 7.38 (d, J=8.07 Hz, 1H) 7.75 (dd, J=7.82, 1.96 Hz, 1H) 7.86 (d, J=9.05 Hz, 2H) 8.02 (d, J=2.20 Hz, 1H) 8.55 (d, J=1.96 Hz, 1H) 8.75 (d, J=2.20 Hz, 1H) 10.16 (s, 1H).

Workup

  1. customThe vial was sealed
  2. customevacuated/purged with argon, and DME (553 μL), water (158 μL) and EtOH (79 μL)
  3. additionwere added
  4. customThe RM was subjected to MW irradiation at 120° C. for 15 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, 15% to 45% in 14 min)

Sources & evidence

ORD record
ord-7c63ae897bf6427abbc25bfe2136e6b6
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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