Chloroacetyl chloride → 4-{3-[5-(4-Fluoro-phenyl)-2-oxo-1,2-dihydro-imidazo[1,2-a]quinolin-8-ylsulfanyl]-phenyl}-tetrahydro-pyran-4-carbonitrile

HRID 2075677Notes

Reaction equation

HRID 2075677 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][C:6]([S:19][C:20]3[CH:21]=[C:22]([C:26]4([C:32]#[N:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[CH:23]=[CH:24][CH:25]=3)=[CH:7][CH:8]=2)[N:3]=1.CCN(C(C)C)C(C)C.Cl[CH2:44][C:45](Cl)=[O:46]>C(Cl)Cl.O>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[C:9]3[C:4](=[CH:5][C:6]([S:19][C:20]4[CH:21]=[C:22]([C:26]5([C:32]#[N:33])[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)[CH:23]=[CH:24][CH:25]=4)=[CH:7][CH:8]=3)[N:3]3[CH2:44][C:45](=[O:46])[N:1]=[C:2]3[CH:11]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 81531Diisopropylethylamine2×HCID 670907114-{3-[2-Amino-4-(4-fluoro-phenyl)-quinolin-7-ylsulfanyl]-phenyl}-tetrahydro-pyran-4-carbonitrile

Product 1

HCID 670908734-{3-[5-(4-Fluoro-phenyl)-2-oxo-1,2-dihydro-imidazo[1,2-a]quinolin-8-ylsulfanyl]-phenyl}-tetrahydro-pyran-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To 3e (120 mg, 0.26 mmol) in CH2Cl2 (3 mL) was added iPr2NEt (0.12 mL, 0.66 mmol), followed by chloroacetyl chloride (0.03 mL, 0.40 mmol), and the reaction was stirred at room temperature. Once complete, the reaction was diluted with water, and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated, and the residue was dissolved in C2H4Cl2. iPr2NEt (0.12 mL, 0.66 mol) was added, and the reaction was sealed and heated to 80° C. overnight. After cooling to room temperature, the reaction was concentrated and purified by preparative HPLC to give the desired product.

Workup

  1. extractionthe aqueous layer was extracted with CH2Cl2
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionthe residue was dissolved in C2H4Cl2
  6. customthe reaction was sealed
  7. temperatureheated to 80° C. overnight
  8. temperatureAfter cooling to room temperature
  9. concentrationthe reaction was concentrated
  10. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-98547a335f3442c7aed14bf728517f3d
Source dataset
uspto-grants-2011_04
Patent number
US07919621B2

Reaction notes

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