N-methyl-2-pyrrolidone → 6-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6,7,8,9-tetrahydro-3,5,6,9a-tetraazabenzo[cd]azulene

HRID 1787022Notes

Reaction equation

HRID 1787022 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[N:26](CCCCl)[CH:25]=[CH:24][C:20]=3[N:21]=[CH:22]N=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.ClC1C=[C:34](C=CC=1OCC1C=CC=C(F)C=1)[NH2:35].CN1CC[CH2:51][C:50]1=O.C(=O)([O-])O.[Na+]>O>[Cl:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:18][C:19]3[CH2:51][CH2:50][N:21]4[CH:22]=[CH:34][N:35]=[C:24]([C:20]=34)[CH:25]=[N:26]2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 516892Sodium BicarbonateHCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 67520636N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine

Product 1

HCID 675209996-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6,7,8,9-tetrahydro-3,5,6,9a-tetraazabenzo[cd]azulene

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine (839 mg), 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (1.10 g) and 1-methyl-2-pyrrolidone (5 mL) was stirred at 140° C. for 1 hr. The reaction mixture was poured into water (10 mL) and adjusted to pH 8 with saturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate (40 mL×3), and the organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel-column chromatography (eluent, hexane:ethyl acetate=60:40→50:50) and further subjected to basic silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100). The object fraction was concentrated under reduced pressure. Chloroform-diisopropyl ether was added to the residue, and the solid was collected by filtration and dried. Recrystallization from ethyl acetate gave the title compound (74.5 mg).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (40 mL×3)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationAfter concentration under reduced pressure
  4. concentrationThe object fraction was concentrated under reduced pressure
  5. additionChloroform-diisopropyl ether was added to the residue
  6. filtrationthe solid was collected by filtration
  7. customdried
  8. customRecrystallization from ethyl acetate

Sources & evidence

ORD record
ord-34250a49fb994af097be8cdb40cc5567
Source dataset
uspto-grants-2009_03
Patent number
US07507740B2

Reaction notes

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