2-Bromopyridine → HCID 118195154, compound

HRID 923858Notes

Reaction equation

HRID 923858 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1.Br[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>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.CCO.O>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:22])([F:24])[F:23])=[CH:18][CH:19]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1

Participants

8

Reactant 4

HCID 79732-BromopyridineHCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 89908040HCID 89908040, compound

Product 1

HCID 118195154HCID 118195154, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

(R)-6-(3-Hydroxypyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 40.1, 150 mg, 0.243 mmol), 2-bromopyridine (192 mg, 1.216 mmol), Pd(Ph3P)2Cl2 (17.07 mg, 0.024 mmol) and Na2CO3 (77 mg, 0.730 mmol) were added to a MW vial and treated with a mixture of DME (1032 μL), water (295 μL) and EtOH (147 μL). The vial was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 20 min. The RM was diluted with DME (2 mL), treated with Si-Thiol (Silicycle, 1.43 mmol/g, 102 mg, 0.146 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 12 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1), from 25% to 100% EtOAc-EtOH+0.1% NH4OH (9:1)) and further purification by preparative HPLC (Condition 13, from 5% to 100% in 14 min) yielded the title compound as a yellow solid. UPLC-MS (condition 1) tR=1.85 min, m/z=445.2 [M+H]+, m/z=443.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.65-1.78 (m, 1H) 1.79-1.94 (m, 1H) 2.85 (d, J=11.49 Hz, 1H) 3.13-3.28 (m, 2H) 3.36-3.50 (m, 1H) 4.19 (d, J=2.20 Hz, 1H) 4.83 (d, J=3.18 Hz, 1H) 7.24-7.44 (m, 3H) 7.53 (d, J=7.82 Hz, 1H) 7.80-7.97 (m, 3H) 8.12 (d, J=2.20 Hz, 1H) 8.66 (dd, J=4.89, 0.73 Hz, 1H) 8.78 (d, J=2.45 Hz, 1H) 10.20 (s, 1H).

Workup

  1. customThe vial was sealed
  2. customevacuated/purged with argon
  3. customsubjected to MW irradiation at 125° C. for 20 min
  4. additionThe RM was diluted with DME (2 mL)
  5. filtrationthe supernatant was filtered
  6. customthe solvent was evaporated off under reduced pressure
  7. customto give a residue which
  8. customwas purified by flash chromatography (RediSep® Silica gel column, 12 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1), from 25% to 100% EtOAc-EtOH+0.1% NH4OH (9:1)) and further purification by preparative HPLC (Condition 13, from 5% to 100% in 14 min)

Sources & evidence

ORD record
ord-ae00ade1ae9c46f5924fc0fefaa39167
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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