Triethylamine → (E)-N-(Methylsulfonyl)-4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzamide hydrochloric acid salt

HRID 1772702Notes

Reaction equation

HRID 1772702 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:29]=[C:30](/[CH:32]=[CH:33]/[C:34]4[CH:43]=[CH:42][C:41]5[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=5)[N:35]=4)[N:31]=3)[C:17]([C:20]3[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][CH:21]=3)=[CH:18][N:19]=2)[CH2:10][CH2:9]1.C(Cl)(=O)C([Cl:47])=O.[CH3:50][S:51]([NH2:54])(=[O:53])=[O:52].CCN(CC)CC>C(Cl)Cl.CN(C1C=CN=CC=1)C.CN(C=O)C>[ClH:47].[CH3:50][S:51]([NH:54][C:24](=[O:25])[C:23]1[CH:22]=[CH:21][C:20]([C:17]2[N:16]3[CH:29]=[C:30](/[CH:32]=[CH:33]/[C:34]4[CH:43]=[CH:42][C:41]5[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=5)[N:35]=4)[N:31]=[C:15]3[C:14]([N:11]3[CH2:10][CH2:9][O:8][CH2:13][CH2:12]3)=[N:19][CH:18]=2)=[CH:28][CH:27]=1)(=[O:53])=[O:52]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 72879MethanesulfonamideHCID 117728004(E)-4-(8-Morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzoic acid trifluoroacetic acid salt

Product 1

HCID 117727912(E)-N-(Methylsulfonyl)-4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzamide hydrochloric acid salt

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To the suspension of compound 57a (160 mg, 0.33 mmol) in DCM (20 mL) was added oxalyl chloride (1.67 mL, 3.35 mmol) dropwise followed by a drop of DMF. The mixture was stirred at rt overnight under an Argon atmosphere. The reaction mixture was concentrated and the orange solid obtained was redissolved in DCM (20 mL). To this solution was added methanesulfonamide (63.7 mg, 0.670 mmol), Et3N (139 μL, 1.00 mmol) and DMAP (40.9 mg, 0.335 mmol). The mixture was stirred at rt for 12 h and concentrated. The residue was dissolved in DCM and extracted with 1N HCl, resulting in an emulsion. The emulsion was concentrated to obtain a residue which was then triturated with MeOH, collected by filtration, and dried to give the title compound 62. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 3.43 (s, 3H), 3.80-3.88 (m, 4H), 4.29-4.45 (m, 4H), 7.55 (s, 1H), 7.78-7.95 (m, 4H), 8.04 (t, J=7.6 Hz, 1H), 8.15 (d, J=8.3 Hz, 2H), 8.19-8.30 (m, 3H), 8.30-8.40 (m, 3H), 8.95 (d, J=8.6 Hz, 1H). Mass Spectrum (LCMS, ESI pos.) Calcd. for C29H26N6O4S: 555.2 [M+H]. found 555.4.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe orange solid obtained
  3. stirringThe mixture was stirred at rt for 12 h
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in DCM
  6. extractionextracted with 1N HCl
  7. customresulting in an emulsion
  8. concentrationThe emulsion was concentrated
  9. customto obtain a residue which
  10. customwas then triturated with MeOH
  11. filtrationcollected by filtration
  12. customdried

Sources & evidence

ORD record
ord-e07a4e5f99834f8dbe97a3a4dc855d1d
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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