p-Chlorophenyl dichlorophosphate → 5-{2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-[(2-hydroxyethyl)amino]-6-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl}-1-methyl-1H-pyrrole-3-carbonitrile

HRID 2222231Notes

Reaction equation

HRID 2222231 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[CH2:12][N:13]1[C:21]([C:22]2[N:26]([CH3:27])[CH:25]=[C:24]([C:28]#[N:29])[CH:23]=2)=[C:20]2[C:15]([N:16]([CH2:32][CH:33]3[CH2:35][CH2:34]3)[C:17](=[O:31])[NH:18][C:19]2=O)=[N:14]1.P(Cl)(Cl)(=O)[O:37][C:38]1[CH:43]=CC(Cl)=CC=1.[N+:48](C1N=CNN=1)([O-])=O>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[CH2:12][N:13]1[C:21]([C:22]2[N:26]([CH3:27])[CH:25]=[C:24]([C:28]#[N:29])[CH:23]=2)=[C:20]2[C:15]([N:16]([CH2:32][CH:33]3[CH2:35][CH2:34]3)[C:17](=[O:31])[N:18]=[C:19]2[NH:48][CH2:43][CH2:38][OH:37])=[N:14]1

Participants

6

Reactant 3

HCID 69879p-Chlorophenyl dichlorophosphateHCID 179901795-{2-[(6-chloroquinolin-4-yl)methyl]-7-cyclopropylmethyl-4,6-dioxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl}-1-methyl-1H-pyrrole-3-carbonitrileHCID 178526901HCID 178526901, compound

Product 1

HCID 100299115-{2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-[(2-hydroxyethyl)amino]-6-oxo-6,7-dihydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl}-1-methyl-1H-pyrrole-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5-{2-[(6-chloroquinolin-4-yl)methyl]-7-cyclopropylmethyl-4,6-dioxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl}-1-methyl-1H-pyrrole-3-carbonitrile (0.42 g) in pyridine (5 mL) were added 4-chlorophenyl phosphorodichloridate (0.5 mL) and 3-nitro-1,2,4 triazole (0.15 g). After heating (Tb=50° C.) for 3 h, the reaction was diluted with ethyl acetate. The organic solution was washed with saturated NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. The residue was dissolved in THF (10 mL) and ethanolamine (1.0 mL). After 3 h, the reaction was concentrated. This residue was purified by flash chromatography using a FlashMaster™ yielding 0.22 g, ES (M+H)+=529.

Workup

  1. washThe organic solution was washed with saturated NaHCO3 and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in THF (10 mL)
  6. concentrationthe reaction was concentrated
  7. customThis residue was purified by flash chromatography
  8. customyielding 0.22 g, ES (M+H)+=529

Sources & evidence

ORD record
ord-5f76ae48d7124edb887d20fd58612c2b
Source dataset
uspto-grants-2008_05
Patent number
US07371757B2

Reaction notes

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