Dichloromethane → HCID 71293778, compound

HRID 2036039Notes

Reaction equation

HRID 2036039 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl.FC(F)(F)S(O[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C@:31]2([OH:48])[C:38]3[N:34]([CH:35]=[N:36][CH:37]=3)[C@@H:33]([C:39]3[CH:44]=[CH:43][C:42]([C:45]#[N:46])=[CH:41][C:40]=3[F:47])[CH2:32]2)[CH:26]=1)(=O)=O>COCCOC.[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[F:47][C:40]1[CH:41]=[C:42]([CH:43]=[CH:44][C:39]=1[C@@H:33]1[N:34]2[CH:35]=[N:36][CH:37]=[C:38]2[C@@:31]([OH:48])([C:27]2[CH:26]=[CH:25][CH:30]=[C:29]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH:28]=2)[CH2:32]1)[C:45]#[N:46]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 86678124HCID 86678124, compound

Product 1

HCID 71293778HCID 71293778, compoundYield 48.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a conical microwave vial was added pyridin-3-ylboronic acid (16 mg, 0.13 mmol), sodium carbonate (18 mg, 0.17 mmol), Pd.dppf.CH2Cl2 (7.0 mg, 0.009 mmol) followed by the addition of a solution of 3-((5R,7S)-5-(4-cyano-2-fluorophenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)phenyl trifluoromethanesulfonate (20 mg, 0.043 mmol) in DME (2 mL). To this crude was added 0.5 ml distilled water. The reaction was carried out under sealed-vessel microwave heating at 120° C. for 10 min using a Biotage Initiator™ (pre-stirring: 60 s, absorption level: very high). Upon completion of the reaction, the mixture was allowed to cool to room temperature, the Pd catalyst was filtered off with a plug of silica using a monster pipet. The solvent was removed. The crude was concentrated and then purified via HPLC, using 10-90% MeCN/H2O to give 8.2 mg of the entitled product. MS 397.1 (M+H); LCMS condition A, retention time 0.92 min. 1H NMR (400 MHz, CDCl3) δ ppm 2.99 (d, 1H), 3.35 (dd, 1H), 5.77 (d, 1H), 6.83 (s, 1H), 7.10-7.22 (m, 1H), 7.23-7.50 (m, 7H), 7.72-7.84 (m, 2H), 8.36-8.49 (m, 1H), 8.59 (s, 1H).

Workup

  1. additionTo this crude was added 0.5 ml
  2. distillationdistilled water
  3. customThe reaction was carried out under sealed-vessel
  4. custom60 s, absorption level
  5. customUpon completion of the reaction
  6. temperatureto cool to room temperature
  7. filtrationthe Pd catalyst was filtered off with a plug of silica using a monster pipet
  8. customThe solvent was removed
  9. concentrationThe crude was concentrated
  10. custompurified via HPLC

Sources & evidence

ORD record
ord-8e53eef7e9de47d7920624be07834a86
Source dataset
uspto-grants-2013_11
Patent number
US08575160B2

Reaction notes

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