1,2-Dimethoxyethane → HCID 89907850, compound

HRID 525656Notes

Reaction equation

HRID 525656 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@@:24]([OH:28])([CH3:27])[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].CC1(C)C(C)(C)OB([C:37]2[N:41]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[N:40]=[CH:39][CH:38]=2)O1.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:28][C@@:24]1([CH3:27])[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:37]3[N:41]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[N:40]=[CH:39][CH:38]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 447552015-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazoleHCID 89907992HCID 89907992, compound

Product 1

HCID 89907850HCID 89907850, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

(S)-5-Bromo-6-(3-hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 13.2, 60 mg, 0.130 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (85 mg, 0.261 mmol), Pd(PPh3)2Cl2 (10.98 mg, 0.016 mmol), Na2CO3 (55.3 mg, 0.521 mmol), DME (553 μL), water (158 μL) and EtOH (79 μL) were added to a MW vial, which 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, 1.44 mmol/g, 54.3 mg, 0.078 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, 4 g, cyclohexane/EtOAc, from 10% to 60% EtOAc) to yield the title compound as a colorless oil. UPLC-MS (Condition 3) tR=1.26 min, m/z=578.3 [M+H]+, m/z=622.3 [M+formic acid-H]−.

Workup

  1. customwas 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, 4 g, cyclohexane/EtOAc, from 10% to 60% EtOAc)

Sources & evidence

ORD record
ord-8cb6b485c7cb45eaa0090c44241e2719
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

Loading…