Tetrahydrofuran → HCID 71008252, compound

HRID 1025591Notes

Reaction equation

HRID 1025591 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:18]=[C:19]([N:23]3[CH:27]=[C:26]([C:28]#[N:29])[C:25]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]([N:39]5[CH2:44][CH2:43][O:42][CH2:41][CH2:40]5)=[O:38])=[CH:33][CH:32]=4)=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C1C[O:48]CC1>O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:18]=[C:19]([N:23]3[CH:27]=[C:26]([C:28]([NH2:29])=[O:48])[C:25]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]([N:39]5[CH2:44][CH2:43][O:42][CH2:41][CH2:40]5)=[O:38])=[CH:33][CH:32]=4)=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 71008260HCID 71008260, compound

Product 1

HCID 71008252HCID 71008252, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1-(3-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile (30 mg, 0.050 mmol) was dissolved in 4 mL of THF and 0.5 mL of water. Then dihydrogen tris(dimethylphosphinito)hydroplatinate (2.3 mg, 0.0052 mmol) was added and the mixture was stirred under fluxing. After 1 hr, TLC indicated complete consumption of the starting material. LC/MS indicated clean desired product formed. The mixture was evaporated and the residue was dissolved in dichloromethane and dried over sodium sulfate, filtered through micron filter and evaporated. The residue was purified through flash column chromatography using methanol in methylene chloride (0% to 5% methanol in 10 minutes, 12 g silica gel) to give 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carboxylic acid amide as a white solid (21 mg, 68% yield). LC/MS clacd for C33H32FN7O4 (m/e) 609.25, obsd 608.0 (M−H, ES−); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (s, 9H), 3.51 (br. s., 4H), 3.59 (br. s., 4H), 7.39 (d, J=8.3 Hz, 3H), 7.56 (d, J=7.8 Hz, 1H), 7.65-7.73 (m, 3H), 7.75-7.86 (m, 3H), 7.89 (s, 1H), 7.98 (br. s., 1H), 8.60 (d, J=2.0 Hz, 1H), 9.04 (s, 1H), 9.42 (s, 1H).

Workup

  1. customconsumption of the starting material
  2. customformed
  3. customThe mixture was evaporated
  4. dissolutionthe residue was dissolved in dichloromethane
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered through micron
  7. filtrationfilter
  8. customevaporated
  9. customThe residue was purified through flash column chromatography
  10. custommethanol in methylene chloride (0% to 5% methanol in 10 minutes, 12 g silica gel)

Sources & evidence

ORD record
ord-2385b6157f9746c3894b9f62eb1baf66
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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