Diisopropylethylamine → tert-Butyl (4-(5-(8-morpholino-2-((quinolin-2-ylthio)methyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)sulfonylcarbamate

HRID 718614Notes

Reaction equation

HRID 718614 reaction equation
FC(F)(F)C(O)=O.[N:8]1([C:14]2[N:19]=[CH:18][C:17]([C:20]3[N:24]4[N:25]=[CH:26][CH:27]=[C:28]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[C:23]4=[N:22][C:21]=3[CH2:35][S:36][C:37]3[CH:46]=[CH:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[N:38]=3)=[CH:16][CH:15]=2)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.CCN(C(C)C)C(C)C.[C:56]([O:60][C:61]([N-:63][S:64](N1C=CC(=[N+](C)C)C=C1)(=[O:66])=[O:65])=[O:62])([CH3:59])([CH3:58])[CH3:57]>C(Cl)Cl>[O:32]1[CH2:33][CH2:34][N:29]([C:28]2[C:23]3[N:24]([C:20]([C:17]4[CH:16]=[CH:15][C:14]([N:8]5[CH2:9][CH2:10][N:11]([S:64]([NH:63][C:61](=[O:62])[O:60][C:56]([CH3:58])([CH3:57])[CH3:59])(=[O:65])=[O:66])[CH2:12][CH2:13]5)=[N:19][CH:18]=4)=[C:21]([CH2:35][S:36][C:37]4[CH:46]=[CH:45][C:44]5[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=5)[N:38]=4)[N:22]=3)[N:25]=[CH:26][CH:27]=2)[CH2:30][CH2:31]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1177285914-(3-(6-(Piperazin-1-yl)pyridin-3-yl)-2-((quinolin-2-ylthio)methyl)imidazo[1,2-b]pyridazin-8-yl)morpholine trifluoroacetic acid saltHCID 178482962HCID 178482962, compound

Product 1

HCID 117732485tert-Butyl (4-(5-(8-morpholino-2-((quinolin-2-ylthio)methyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazin-1-yl)sulfonylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compound 6 (137 mg, 0.612 mmol) was placed in an 8 mL vial equipped with a stir bar and then DCM (1 mL) and DIEA (68.2 μL, 0.486 mmol) were added. (tert-Butoxycarbonyl)((4-(dimethyliminio)pyridin-1(4H)-yl)sulfonyl)amide (48.8 mg, 0.162 mmol) was added as a solid and the reaction was stirred at rt for 3 h and then the solvent was removed under reduced pressure. The crude product was chromatographed on a 12 g SiO2 pre-packed column eluting with 0-100% EtOAc/heptane. The resulting product was chromatographed on a 12 g SiO2 pre-packed column eluting with 0-80% EtOAc/heptane to afford the title compound 31a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.55 (d, J=2.2 Hz, 1H), 7.96 (d, J=5.6 Hz, 1H), 7.80-7.92 (m, 3H), 7.71 (d, J=8.1 Hz, 1H), 7.58-7.66 (m, 1H), 7.29-7.48 (m, 2H), 7.24 (d, J=8.8 Hz, 1H), 6.70 (d, J=8.8 Hz, 1H), 6.04 (d, J=5.9 Hz, 1H), 4.85 (s, 2H), 3.89-4.00 (m, 4H), 3.80-3.89 (m, 4H), 3.62-3.73 (m, 4H), 1.47 (s, 9H).

Workup

  1. customvial equipped with a stir bar
  2. customthe solvent was removed under reduced pressure
  3. customThe crude product was chromatographed on a 12 g SiO2 pre-packed column
  4. washeluting with 0-100% EtOAc/heptane
  5. customThe resulting product was chromatographed on a 12 g SiO2 pre-packed column
  6. washeluting with 0-80% EtOAc/heptane

Sources & evidence

ORD record
ord-a9fd3152af61413cae1487d06d8cd6f3
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

Loading…