Triethylamine → HCID 90019290, compound

HRID 591388Notes

Reaction equation

HRID 591388 reaction equation
[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[N:10][C:11]([C:17]2[CH:18]=[C:19]([S:23]([NH2:26])(=[O:25])=[O:24])[CH:20]=[N:21][CH:22]=2)=[N:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N([CH2:40][CH3:41])CC)C.[P:42](Cl)(=[O:49])([O:46][CH2:47][CH3:48])[O:43][CH2:44][CH3:45]>C(Cl)(Cl)Cl.CN(C)C1C=CN=CC=1.C(Cl)Cl.O>[CH2:44]([O:43][P:42]([N:26]([S:23]([C:19]1[CH:20]=[N:21][CH:22]=[C:17]([C:11]2[N:10]=[C:9]([NH:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:8]3[C:13](=[CH:14][CH:15]=[CH:16][C:7]=3[C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:12]=2)[CH:18]=1)(=[O:24])=[O:25])[P:42](=[O:43])([OH:49])[O:46][CH2:40][CH3:41])([O:46][CH2:47][CH3:48])=[O:49])[CH3:45]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 13139Diethyl chlorophosphateHCID 510307305-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridine-3-sulfonamide

Product 1

HCID 90019290HCID 90019290, compoundYield 20%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridine-3-sulfonamide (1) (0.150 g, 0.320 mmol) in CHCl3 (10 mL) was added triethylamine (0.268 mL, 1.92 mmol) followed by 4-dimethylaminopyridine (7.8 mg, 0.064 mmol) under nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 5 min and diethyl phosphorochloridate (0.331 g, 1.92 mmol) was added dropwise. The reaction mixture was allowed to warm up to room temperature and stirred overnight. The reaction mixture was diluted with DCM (20 mL) and water (20 mL), and extracted with DCM (3×50 mL). The combined organic layers were washed with water and brine and dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by HPLC purification to afford ethyl hydrogen diethoxyphosphoryl((5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonyl)phosphoramidate (9) (0.045 g, 0.063 mmol, 20% yield) as a yellow solid. Preparative (Water mass) HPLC Conditions: Column: Atlantis dc18 (19×250 mm) 10 μm, Mobile Phase A: 10 mm ammonium acetate. Mobile Phase B: acetonitrile, Gradient: 10 to 60% B over 10 min, Flow Rate: 15 mL/min., Retention time: 11.35 min.; 1H NMR (400 MHz, chloroform-d) (δ ppm) 1.20-1.34 (m, 9H) 4.06-4.22 (m, 6H) 4.60-4.77 (m, 2H) 6.63 (br. s., 1H) 7.09-7.20 (m, 3H), 7.44-7.54 (m, 5H) 7.61-7.72 (m, 2H) 7.85-7.96 (m, 1H) 8.42 (d, J=4.02 Hz, 1H) 9.21 (dd, J=6.78, 2.01 Hz, 2H) 9.67 (d, J=2.01 Hz, 1H); LCMS Method D: retention time 1.56 min, [M+l]=713.2.

Workup

  1. temperatureto warm up to room temperature
  2. stirringstirred overnight
  3. extractionextracted with DCM (3×50 mL)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by HPLC purification

Sources & evidence

ORD record
ord-f96931d18721440fad30aa1942322e37
Source dataset
uspto-grants-2016_01
Patent number
US09238666B2

Reaction notes

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