1,4-Dibromobutane → 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one

HRID 20652Notes

Reaction equation

HRID 20652 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([Cl:25])[C:9]=1[NH:10][C:11]1[C:20]2[C:15](=[C:16]([OH:23])[C:17]([O:21][CH3:22])=[CH:18][CH:19]=2)[O:14][C:13](=[O:24])[CH:12]=1.[Br:26][CH2:27][CH2:28][CH2:29][CH2:30]Br.OP([O-])(O)=O.[K+]>CS(C)=O>[Br:26][CH2:27][CH2:28][CH2:29][CH2:30][O:23][C:16]1[C:17]([O:21][CH3:22])=[CH:18][CH:19]=[C:20]2[C:15]=1[O:14][C:13](=[O:24])[CH:12]=[C:11]2[NH:10][C:9]1[C:8]([Cl:25])=[CH:7][N:6]=[CH:5][C:4]=1[Cl:3]

Participants

6

Reactant 4

HCID 80561,4-DibromobutaneHCID 24758Sodium hydrideHCID 516951Monobasic potassium phosphateHCID 248495704-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one

Product 1

HCID 248495678-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Sodium hydride (31 mg, 0.78 mmol) was added to a solution of 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one (111 mg, 0.31 mmol, Example 29) and DMSO (2 mL) at rt under N2. After 5 min, 1,4-dibromobutane (0.05 mL, 0.42 mmol) was added. After 3 h, the reaction was poured into 1M KH2PO4 (30 mL) and extracted with ethyl acetate (40 mL×2). The combined extracts were dried, filtered, concentrated, and purified by silica gel chromatography (3:2→1:4; hexanes:ethyl acetate) to give 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one: 1H NMR (400 MHz, DMSO-d6): δ 9.51 (s, 1H), 8.81 (s, 2H), 7.95 (d, 1H), 7.21 (d, 1H), 4.64 (s, 1H), 4.01 (t, 2H), 3.92 (s, 3H), 3.63 (t, 2H), 2.05 (m, 2H), 1.80 (m, 2H); MS (ESI): 486.8.

Workup

  1. waitAfter 3 h
  2. extractionextracted with ethyl acetate (40 mL×2)
  3. customThe combined extracts were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (3:2→1:4; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-2107d794a1664ddb940b2a49e7012c71
Source dataset
uspto-grants-2010_06
Patent number
US07745646B2

Reaction notes

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