N,N-Diethylethanamine trihydrofluoride → 1-cyclopropyl-3-((3-(4-fluorobutyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one

HRID 80633Notes

Reaction equation

HRID 80633 reaction equation
F[B-](F)(F)F.C(N([S+](F)[F:12])CC)C.[CH:14]1([N:17]2[C:25]3[CH:24]=[CH:23][N:22]=[CH:21][C:20]=3[N:19]([CH2:26][C:27]3[N:28]=[C:29]4[CH:34]=[N:33][CH:32]=[CH:31][N:30]4[C:35]=3[CH2:36][CH2:37][CH2:38][CH2:39]O)[C:18]2=[O:41])[CH2:16][CH2:15]1.F.F.F.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:14]1([N:17]2[C:25]3[CH:24]=[CH:23][N:22]=[CH:21][C:20]=3[N:19]([CH2:26][C:27]3[N:28]=[C:29]4[CH:34]=[N:33][CH:32]=[CH:31][N:30]4[C:35]=3[CH2:36][CH2:37][CH2:38][CH2:39][F:12])[C:18]2=[O:41])[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 175505N,N-Diethylethanamine trihydrofluorideHCID 516892Sodium BicarbonateHCID 44517918(Diethylamino)(difluoro)sulfanium tetrafluoroborateHCID 574102501-cyclopropyl-3-((3-(4-hydroxybutyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one

Product 1

HCID 574102511-cyclopropyl-3-((3-(4-fluorobutyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2(3H)-oneYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of diethylaminodifluorosulfonium tetrafluoroborate (453 mg, 1.982 mmole), 1-cyclopropyl-3-((3-(4-hydroxybutyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one P17 (500 mg, 1.321 mmole), and triethylamine trihydrofluoride (319 mg, 1.5 eq) in DCM (20 mL) was stirred at RT under N2 atmosphere for 60 minutes. 100 mL sat NaHCO3 was then added and the mixture was stirred until gas evolution stopped (10 minutes), then was extracted with 150 mL DCM (2×). Combined organic layers were dried on Na2SO4, filtrated and evaporated to dryness. Purification by Prep HPLC on (RP Vydac Denali C18-10 μm, 250 g, 5 cm) with (0.25% NH4HCO3 solution in water, MeOH) as mobile phase, afforded the target compound P18 in 20% yield. m/z=381 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.82-0.92 (m, 2H), 1.00-1.10 (m, 2H), 1.46-1.80 (m, 4H), 2.95 (tdd, J=6.96, 6.96, 3.64, 3.51 Hz, 1H), 3.12 (t, J=7.53 Hz, 2H), 4.43 (dt, J=47.43, 6.00 Hz, 2H), 5.23 (s, 2H), 7.24 (dd, J=5.27, 0.75 Hz, 1H), 7.89 (d, J=4.52 Hz, 1H), 8.22 (d, J=5.27 Hz, 1H), 8.41 (s, 1H), 8.47 (dd, J=4.77, 1.51 Hz, 1H), 8.98 (d, J=1.51 Hz, 1H).

Workup

  1. additionwas then added
  2. stirringthe mixture was stirred until gas evolution
  3. custom(10 minutes)
  4. extractionwas extracted with 150 mL DCM (2×)
  5. customCombined organic layers were dried on Na2SO4
  6. filtrationfiltrated
  7. customevaporated to dryness
  8. customPurification by Prep HPLC on (RP Vydac Denali C18-10 μm, 250 g, 5 cm) with (0.25% NH4HCO3 solution in water, MeOH) as mobile phase
  9. customafforded the target compound P18 in 20% yield

Sources & evidence

ORD record
ord-9531dc6ba35941ac88faff43a8e8543f
Source dataset
uspto-grants-2014_09
Patent number
US08846672B2

Reaction notes

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