Triethylamine → HCID 178477720, compound

HRID 536274Notes

Reaction equation

HRID 536274 reaction equation
[CH2:1]([S:3](Cl)(=[O:5])=[O:4])[CH3:2].[NH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[CH:14][C:15]2[C:16]3[N:17]([CH2:33][CH2:34][N:35]=3)[C:18]([NH:24][C:25](=[O:32])[C:26]3[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=3)=[N:19][C:20]=2[C:21]=1[O:22][CH3:23].C(N(CC)CC)C>ClCCl.CN(C)C=O>[CH2:1]([S:3]([NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[CH:14][C:15]2[C:16]3[N:17]([CH2:33][CH2:34][N:35]=3)[C:18]([NH:24][C:25](=[O:32])[C:26]3[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=3)=[N:19][C:20]=2[C:21]=1[O:22][CH3:23])(=[O:5])=[O:4])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11667Ethanesulfonyl chloride2×HCID 178493868HCID 178493868, compound

Product 1

HCID 178477720HCID 178477720, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Ethanesulfonyl chloride (18 mg, 0.14 mmol) was diluted in dichloromethane (5 ml) and cooled to 0° C. A solution of N-[8-(3-amino-propyloxy)-7-methoxy-2,3-dihydro-imidazo[1,2-c]quinazolin-5-yl]-nicotinamide hydrotrifluoroacetate (Step 2, 50 mg, 0.13 mmol) in dimethylformamide (5 mL) was added dropwise, and the mixture was stirred at −10° C. for 30 min. Triethylamine (0.07 mL) was added dropwise, and stirring was continued at −10° C. for another 30 min. The reaction mixture was stirred at rt overnight. Another equivalent of ethanesulfonyl chloride was added, and the mixture was stirred at rt for 12 h. The reaction mixture was quenched by the addition of water, and was extracted with dichloromethane. The combined organic extracts were concentrated to afford a white solid, which was triturated with ethyl acetate to remove residual dimethylformamide. After filtration the solid was carefully washed with water and dried in a vacuum oven. The title compound was obtained as a white solid (4.2 mg, 6.8%). HPLC MS RT=1.63 min, MH+=487.3. 1H NMR (DMSO-d6+2 drops TFA-d) δ: 1.18 (3H, t), 2.00 (2H, m), 2.99 (2H, quartet), 3.14 (2H, t), 4.01 (3H, s), 4.23-4.34 (4H, m), 4.57 (2H, m), 7.49 (1H, d), 7.91 (1H, m), 8.04 (1H, d), 8.95 (1H, m), 8.96 (1H, m), 9.49 (1H, m).

Workup

  1. stirringstirring
  2. waitwas continued at −10° C. for another 30 min
  3. stirringThe reaction mixture was stirred at rt overnight
  4. stirringthe mixture was stirred at rt for 12 h
  5. customThe reaction mixture was quenched by the addition of water
  6. extractionwas extracted with dichloromethane
  7. concentrationThe combined organic extracts were concentrated
  8. customto afford a white solid, which
  9. customwas triturated with ethyl acetate
  10. customto remove residual dimethylformamide
  11. filtrationAfter filtration the solid
  12. washwas carefully washed with water
  13. customdried in a vacuum oven

Sources & evidence

ORD record
ord-25d9f86e4b4e44eaa7d46733e83e0b2c
Source dataset
uspto-grants-2014_10
Patent number
US08859572B2

Reaction notes

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