Tert-Butylamine → HCID 71730504, compound

HRID 1056216Notes

Reaction equation

HRID 1056216 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([C:12]3[NH:20][C:19]4[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=4[CH:13]=3)[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:22][C:23]([NH2:26])([CH3:25])[CH3:24]>CN1C(=O)CCC1.C(Cl)Cl>[C:23]([NH:26][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([C:12]3[NH:20][C:19]4[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=4[CH:13]=3)[CH:6]=[CH:7][CH:8]=2)[N:3]=1)([CH3:25])([CH3:24])[CH3:22]

Participants

5

Reactant 2

HCID 6385Tert-ButylamineHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 71730504HCID 71730504, compoundYield 21.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (1) (125 mg, 0.42 mmol) and 2-methylpropan-2-amine (154 mg, 2.10 mmol) (Sigma-Aldrich) in NMP (0.84 mL) was heated in a sealed tube at 165° C. for 2.5 d. The reaction mixture was diluted with DCM (100 mL), added to a separatory funnel, and washed with saturated aq. brine (4×100 mL) before the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 1-4% of 2 M NH3 in MeOH/DCM to give 2-(2-(tert-butylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (30 mg) (0.09 mmol, 21% yield) as a yellow oil which was slightly impure. This material was dissolved in MeOH (˜20 mg/mL) and injected (2×1.0 mL) onto the Shimadzu preparatory LC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% MeCN/water with 0.1% TFA); the pure fractions were combined, basicified with NaHCO3 (saturated, aq.), extracted with CHCl3/IPA(3:2), separated, dried over Na2SO4, and concentrated via rotary evaporation to give 2-(2-(tert-butylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (340) (19 mg, 0.08 mmol, 14% yield) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.62 (s, 9H) 2.99 (t, J=6.94 Hz, 2H) 3.65 (td, J=6.85, 2.35 Hz, 2H) 4.84 (s, 1H) 5.71 (br. s., 1H) 6.56 (d, J=9.00 Hz, 1H) 7.10 (d, J=1.76 Hz, 1H) 7.21 (t, J=7.73 Hz, 1H) 7.38 (d, J=7.63 Hz, 1H) 7.75 (d, J=9.00 Hz, 1H) 7.96 (d, J=7.63 Hz, 1H) 13.24 (br. s., 1H). MS (ESI, pos. ion) m/z: 353.3 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with saturated aq. brine (4×100 mL) before the organic layer
  3. customwas separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customwas purified

Sources & evidence

ORD record
ord-9ee0a85ad3a3423fb5404c489afe943d
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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