Dicyclohexylcarbodiimide → N-Methanesulfonyl-5-[8-(morpholin-4-yl)-2-[(quinolin-2-yloxy)methyl]imidazo[1,2-a]pyrazin-5-yl]pyridine-2-carboxamide

HRID 1772622Notes

Reaction equation

HRID 1772622 reaction equation
[N:1]1([C:7]2[C:8]3[N:9]([CH:22]=[C:23]([CH2:25][O:26][C:27]4[CH:36]=[CH:35][C:34]5[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=5)[N:28]=4)[N:24]=3)[C:10]([C:13]3[CH:14]=[CH:15][C:16]([C:19](O)=[O:20])=[N:17][CH:18]=3)=[CH:11][N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:37][S:38]([NH2:41])(=[O:40])=[O:39].C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:37][S:38]([NH:41][C:19]([C:16]1[CH:15]=[CH:14][C:13]([C:10]2[N:9]3[CH:22]=[C:23]([CH2:25][O:26][C:27]4[CH:36]=[CH:35][C:34]5[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=5)[N:28]=4)[N:24]=[C:8]3[C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)=[N:12][CH:11]=2)=[CH:18][N:17]=1)=[O:20])(=[O:40])=[O:39]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 72879MethanesulfonamideHCID 117728195HCID 117728195, compound

Product 1

HCID 86346078N-Methanesulfonyl-5-[8-(morpholin-4-yl)-2-[(quinolin-2-yloxy)methyl]imidazo[1,2-a]pyrazin-5-yl]pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 15c (400 mg, 0.790 mmol) in DCM (20 mL) was added methanesulfonamide (78.8 mg, 0.830 mmol), DCC (256 mg, 1.24 mmol) and 4-dimethylaminopyridine (152 mg, 1.24 mmol). The reaction mixture was stirred at rt overnight, and was quenched with H2O (40 mL). The resulting mixture was extracted with DCM (3×40 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with DCM/MeOH (10:1 v/v). The title compound 76 was obtained as a yellow solid (307 mg, 69% yield). 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 8.99 (s, 1H), 8.27-8.19 (m, 3H), 8.08 (s, 1H), 7.89 (d, J=7.8 Hz, 1H), 7.79 (d, J=8.4 Hz, 1H), 7.68 (t, J=6.9 Hz, 1H), 7.56 (s, 1H), 7.47 (t, J=6.9 Hz, 1H), 7.05 (d, J=8.7 Hz, 1H), 5.58 (s, 2H), 4.41-4.20 (m, 4H), 3.88-3.71 (m, 4H), 3.05 (s, 3H). Mass Spectrum (LCMS, ESI pos.): Calcd. for C27H25N7O5S: 560.2 (M+H). Found 560.0.

Workup

  1. customwas quenched with H2O (40 mL)
  2. extractionThe resulting mixture was extracted with DCM (3×40 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by flash column chromatography on silica gel
  7. washeluting with DCM/MeOH (10:1 v/v)

Sources & evidence

ORD record
ord-56d4b9112c5e41068eb54f57b81cb4f9
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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