Water → HCID 87421770, compound

HRID 1256217Notes

Reaction equation

HRID 1256217 reaction equation
[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])[C:9]3[CH:10]=[C:11]([CH:15]=[O:16])[CH:12]=[CH:13][C:14]=3[C:5]=2[NH:4][N:3]=1.O.[CH3:26][Si:27]([CH3:34])([CH3:33])[CH2:28][CH2:29][O:30][CH2:31]Cl>CN(C=O)C.C(N(C(C)C)CC)(C)C>[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])[C:9]3[CH:10]=[C:11]([CH:15]=[O:16])[CH:12]=[CH:13][C:14]=3[C:5]=2[N:4]([CH2:31][O:30][CH2:29][CH2:28][Si:27]([CH3:34])([CH3:33])[CH3:26])[N:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178519296HCID 178519296, compound

Product 1

HCID 87421770HCID 87421770, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A 150 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 780 mg of 3-bromo-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde in 20 ml of DMF, 2.5 ml of diisopropylethylamine and 0.75 ml of 2-(trimethylsilyl)ethoxymethyl chloride. The mixture is stirred at RT for 24 h and then poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. This gives 1.18 g of a crude product, which is purified by chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (99.5/0.5 by vol.), to give on one hand 545 mg of 3-bromo-5-(2,6-difluorophenyl)-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde in the form of a cream solid: MS (E/I): m/z=388 (M+); 1H NMR: −0.13 (s, 9H); 0.86 (t, J=7.8 Hz, 2H); 3.66 (t, J=7.8 Hz, 2H); 618 (s, 2H); 7.43 (t, J=7.9 Hz, 2H); 7.79 (m, 1H); 8.39 (broad s, 1H) 8.48 (dd, J=8.3, 1.5 Hz, 1H) 8.80 (d, J=8.3 Hz, 1H) 10.17 (s, 1H), and on the other hand 354 mg of 3-bromo-5-(2,6-difluorophenyl)-2-(2-trimethylsilanylethoxymethyl)-2H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde (cream solid). MS (E/I): m/z=388 (M+); 1H NMR: −0.08 (s, 9H); 0.90 (t, J=8.0 Hz, 2H); 3.73 (t, J=8.0 Hz, 2H); 5.91 (s, 2H); 7.41 (t, J=7.8 Hz, 2H); 7.77 (m, 1H); 8.22 (broad s, 1H) 8.42 (dd, J=8.3, 1.5 Hz, 1H) 8.72 (d, J=8.3 Hz, 1H) 10.13 (s, 1H).

Workup

  1. customA 150 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. extractionextracted with AcOEt
  3. washwashed with saturated NaCl solution
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under RP
  7. customThis gives 1.18 g of a crude product, which is purified by chromatography on silica gel (20-45 μm)
  8. washeluting with a mixture of DCM and methanol (99.5/0.5 by vol.)

Sources & evidence

ORD record
ord-b612fcb4f3434bf6b0bccdcec16bede5
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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