Diisopropylethylamine → N-((4-(8-Morpholino-2-(2-(quinolin-2-yl)ethyl)imidazo[1,2-a]pyrazin-5-yl)phenyl)carbamoyl)methanesulfonamide

HRID 1772705Notes

Reaction equation

HRID 1772705 reaction equation
FC(F)(F)C(O)=O.[O:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]3[N:16]([CH:27]=[C:28]([CH2:30][CH2:31][C:32]4[CH:41]=[CH:40][C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[N:33]=4)[N:29]=3)[C:17]([C:20]3[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=3)=[CH:18][N:19]=2)[CH2:10][CH2:9]1.[CH3:42][S:43]([NH:46][C:47](=O)[O:48]CC)(=[O:45])=[O:44].CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[O:8]1[CH2:9][CH2:10][N:11]([C:14]2[C:15]3[N:16]([CH:27]=[C:28]([CH2:30][CH2:31][C:32]4[CH:41]=[CH:40][C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[N:33]=4)[N:29]=3)[C:17]([C:20]3[CH:26]=[CH:25][C:23]([NH:24][C:47]([NH:46][S:43]([CH3:42])(=[O:45])=[O:44])=[O:48])=[CH:22][CH:21]=3)=[CH:18][N:19]=2)[CH2:12][CH2:13]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1201508(Methylsulfonyl)-carbamic acid ethyl esterHCID 1177278994-(8-Morpholino-2-(2-(quinolin-2-yl)ethyl)imidazo[1,2-a]pyrazin-5-yl)aniline trifluoroacetic acid salt

Product 1

HCID 117728153N-((4-(8-Morpholino-2-(2-(quinolin-2-yl)ethyl)imidazo[1,2-a]pyrazin-5-yl)phenyl)carbamoyl)methanesulfonamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of compound 59a (100 mg, 0.147 mmol) and ethyl methylsulfonylcarbamate (148 mg, 0.888 mmol) and DIEA (0.191 mL, 1.11 mmol) in DMF (2 mL) was stirred at 100° C. for 2 h. The reaction mixture was allowed to cool to rt and diluted with DCM. The reaction mixture was concentrated and the residue obtained was purified by flash column chromatography on silica gel (0-20% MeOH/EtOAc), recrystallized with EtOAc/heptanes and purified by prep-TLC (1:5:5 MeOH/DCM/EtOAc) to give the title compound 40. 1H-NMR (400 MHz, CDCl3) δ (ppm): 3.22-3.30 (m, 2H), 3.33 (s, 3H), 3.37-3.47 (m, 2H), 3.69-3.87 (m, 4H), 4.03-4.21 (m, 4H), 7.16 (s, 1H), 7.31 (s, 1H), 7.28 (s, 1H), 7.39 (d, J=8.3 Hz, 1H), 7.43-7.60 (m, 3H), 7.67-7.76 (m, 1H), 7.82 (d, J=7.6 Hz, 1H), 8.05 (d, J=8.3 Hz, 1H), 8.15 (d, J=8.3 Hz, 1H), 8.81 (br. s., 1H). Mass Spectrum LCMS, ESI (pos.) Calcd. for C29H29N7O4S: 572.2 [M+H]. found 572.5.

Workup

  1. temperatureto cool to rt
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue obtained
  4. customwas purified by flash column chromatography on silica gel (0-20% MeOH/EtOAc)
  5. customrecrystallized with EtOAc/heptanes
  6. custompurified by prep-TLC (1:5:5 MeOH/DCM/EtOAc)

Sources & evidence

ORD record
ord-93b83ec492ef4d5ab664e5a48677f2df
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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