Bromomethylcyclopropane → 6-Bromo-1-(cyclopropylmethyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine

HRID 2205898Notes

Reaction equation

HRID 2205898 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Br:11][C:12]1[N:17]=[CH:16][C:15]2[CH:18]=[C:19]([C:21]3[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=3)[NH:20][C:14]=2[CH:13]=1.Br[CH2:28][CH:29]1[CH2:31][CH2:30]1>CN(C=O)C.O.CCOC(C)=O>[Br:11][C:12]1[N:17]=[CH:16][C:15]2[CH:18]=[C:19]([C:21]3[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=3)[N:20]([CH2:28][CH:29]3[CH2:31][CH2:30]3)[C:14]=2[CH:13]=1

Participants

7

Reactant 3

HCID 81503BromomethylcyclopropaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 867062766-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine

Product 1

HCID 867063096-Bromo-1-(cyclopropylmethyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

NaHMDS (173 mL, 0.173 mmol) was added to a solution of 6-bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine (Preparation 22, 40 mg, 0.144 mmol) in DMF (630 mL). The reaction mixture was stirred for 15 minutes at 60° C. before the addition of (bromomethyl)cyclopropane (21 mL, 0.217 mmol). The reaction was then stirred for 24 hours at 60° C. before being diluted with water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude was purified via Biotage silica gel column chromatography eluting with DCM/EtOAc (99/1 to 80/20) to afford a colourless oil as the title compound. (29 mg, 61%). 1H NMR (500 MHz, CDCl3) d 0.21-0.24 (m, 2H), 0.52-0.56 (m, 2H), 1.08-1.15 (m, 1H), 4.02 (s, 3H), 4.06 (d, J=6.3 Hz, 2H), 6.54 (d, J=0.9 Hz, 1H), 7.45 (t, J=0.9 Hz, 1H), 7.61 (d, J=0.8 Hz, 1H), 7.70 (d, J=0.8 Hz, 1H), 8.60 (d, J=0.9 Hz, 1H). LC (Method B)-MS (ESI, m/z) tR 2.64 min, 331 [(M+H+), 100%].

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified via Biotage silica gel column chromatography
  7. washeluting with DCM/EtOAc (99/1 to 80/20)

Sources & evidence

ORD record
ord-58dfd837269343c195f8fbf6913097b1
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

Loading…