Tetrahydrofuran → HCID 178519657, compound

HRID 505543Notes

Reaction equation

HRID 505543 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]3[N:18]=[N:17][N:16]([CH2:20][C:21]4[C:29]5[C:24](=[N:25][CH:26]=[CH:27][CH:28]=5)[NH:23][N:22]=4)[C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:30])[CH:9]=1)[C:5]#N.[H-].[H-].[H-].[H-].[Li+].[Al+3].C1C[O:40]CC1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]3[N:18]=[N:17][N:16]([CH2:20][C:21]4[C:29]5[C:24](=[N:25][CH:26]=[CH:27][CH:28]=5)[NH:23][N:22]=4)[C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:30])[CH:9]=1)[CH:5]=[O:40]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 21226445Aluminium lithium hydrideHCID 178509924HCID 178509924, compound

Product 1

HCID 178519657HCID 178519657, compound

Procedure

To 3-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-1,2,3-benzotriazol-4-yl]oxy}benzonitrile (10 mg, 0.023 mmol) dissolved in dry THF (0.5 mL) at 0° C. was added LAH solution 1M in THF (0.046 mL, 0.046 mmol). After 30 minutes, the reaction was quenched with EtOAc (2 mL) at 0° C., followed by addition of saturated aqueous Na2SO4 (0.25 mL), and then after 5 minutes by addition of water (0.5 mL). This mixture was allowed to stir for 5 minutes after which time solid Na2SO4 was added to the reaction mixture. The dried mixture was then filtered and solvent removed under reduced pressure. The resulting residue was purified by reverse phase chromatography eluting with 30-95% MeCN/H2O+0.1% TFA. Product fractions were lyophilized to afford the title compound. 1H NMR (DMSO-d6) δ 9.90 (s, 1H), 8.52 (d, J=3.5 Hz), 8.10 (d, J=7.5 Hz), 7.90 (d, J=8.9 Hz, 1H), 7.80 (d, J=8.9 Hz, 1H), 7.72 (m, 1H), 7.30 (m, 1H), 7.20 (dd, J=8.1 Hz, J=4.6 Hz, 1H), 6.40 (s, 2H).

Workup

  1. customthe reaction was quenched with EtOAc (2 mL) at 0° C.
  2. additionfollowed by addition of saturated aqueous Na2SO4 (0.25 mL)
  3. additionafter 5 minutes by addition of water (0.5 mL)
  4. additionwas added to the reaction mixture
  5. filtrationThe dried mixture was then filtered
  6. customsolvent removed under reduced pressure
  7. customThe resulting residue was purified by reverse phase chromatography
  8. washeluting with 30-95% MeCN/H2O+0.1% TFA

Sources & evidence

ORD record
ord-2cc0e485a1c6413e8cba5c14cbbfcbb0
Source dataset
uspto-grants-2010_08
Patent number
US07781454B2

Reaction notes

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