Ethylenediamine → HCID 89907600, compound

HRID 525655Notes

Reaction equation

HRID 525655 reaction equation
[OH:1][C@@:2]1([CH3:40])[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:27]3[N:31](COCC[Si](C)(C)C)[N:30]=[CH:29][CH:28]=3)=[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.C(N)CN.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CCOC(C)=O>[OH:1][C@@:2]1([CH3:40])[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:27]3[NH:31][N:30]=[CH:29][CH:28]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:24])([F:22])[F:23])=[CH:18][CH:19]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 89907850(S)-6-(3-Hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)nicotinamide

Product 1

HCID 89907600HCID 89907600, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

(S)-6-(3-Hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)nicotinamide (Stage 13.1), ethylenediamine (57.3 μL, 0.848 mmol) and 1 M TBAF in THF (848 μL, 0.848 mmol) was added to a MW vial, which was sealed and the RM was stirred at 80° C. for 24 h. The solvent was evaporated off under reduced pressure to give a residue which was dissolved in EtOAc (30 mL), washed 3 times with sat. aq. NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product was purified by preparative SFC (Column 2-EP, from 20% to 25% in 6 min) to yield the title compound as a white solid. HPLC Chiral (CHIRALCEL® OD-H, 250×4.6 mm, eluent: n-heptane/EtOH/MeOH (80:12:8), 1 mL/min, UV 210 nm) tR=13.92 min, UPLC-MS (Condition 3) tR=0.93 min, m/z=448.2 [M+H]+, m/z=446.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.19 (s, 3H) 1.65-1.81 (m, 2H) 3.01 (d, J=11.54 Hz, 1H) 3.07 (d, J=10.92 Hz, 1H) 3.24-3.33 (m, 1H) 3.43-3.53 (m, 1H) 4.64-4.75 (m, 1H) 6.34-6.41 (m, 1H) 7.34 (d, J=8.66 Hz, 2H) 7.52-7.84 (m, 1H) 7.86 (d, J=9.16 Hz, 2H) 8.00-8.07 (m, 1H) 8.69-8.78 (m, 1H) 10.19 (s, 1H) 12.89-13.13 (m, 1H).

Workup

  1. customwas sealed
  2. customThe solvent was evaporated off under reduced pressure
  3. customto give a residue which
  4. washwashed 3 times with sat. aq. NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated off under reduced pressure
  7. customto give a crude product
  8. customwas purified by preparative SFC (Column 2-EP, from 20% to 25% in 6 min)

Sources & evidence

ORD record
ord-2958a073a62e4e1bb5cef2b92077de83
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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