Tetrabutylammonium Fluoride → HCID 86345168, compound

HRID 711184Notes

Reaction equation

HRID 711184 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:25][C:26]([NH:28][C@@H:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C@H:32]([O:39][C:40]3[CH:41]=[CH:42][C:43]4[N:44]([C:46]([C@@H:49]5[CH2:53][CH2:52][CH2:51][N:50]5[CH3:54])=[N:47][N:48]=4)[CH:45]=3)[CH2:31][CH2:30]2)=[O:27])[N:8]([C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[C:12]([O:17][Si](C(C)(C)C)(C)C)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[C:1]([C:5]1[CH:6]=[C:7]([NH:25][C:26]([NH:28][C@@H:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C@H:32]([O:39][C:40]3[CH:41]=[CH:42][C:43]4[N:44]([C:46]([C@@H:49]5[CH2:53][CH2:52][CH2:51][N:50]5[CH3:54])=[N:47][N:48]=4)[CH:45]=3)[CH2:31][CH2:30]2)=[O:27])[N:8]([C:10]2[CH:11]=[C:12]([OH:17])[CH:13]=[C:14]([Cl:16])[CH:15]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 1233369991-{5-tert-Butyl-2-[3-(tert-butyl-dimethyl-silanyloxy)-5-chloro-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

Product 1

HCID 86345168HCID 86345168, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of Intermediate 62e (265 mg, 0.32 mmol) and TBAF (1M in THF, 0.38 mL, 0.38 mmol) in THF (3 mL) was stirred at RT for 1.3 h, then diluted with water and extracted with DCM. The combined organics were dried and concentrated in vacuo. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to give the impure product. This residue was purified further by HPLC (XBridge C18 column, 35-98% MeCN in H2O, 0.1% NH4OH) to give the product. This residue purified further by HPLC (XBridge C18 column, 20-98% MeCN in H2O, 0.1% NH4OH) to give the title compound (63 mg, 30%). LCMS (Method 5): Rt 3.61 min, m/z 655 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.27 (9H, s), 1.93-2.12 (5H, m), 2.13 (3H, s), 2.14-2.25 (3H, m), 2.34-2.37 (1H, m), 3.12-3.15 (1H, m), 3.99 (1H, t, J=8.2 Hz), 4.80-4.83 (1H, m), 5.39 (1H, t, J=4.2 Hz), 6.31 (1H, s), 6.78 (1H, s), 6.89 (1H, s), 6.96 (1H, s), 7.15 (1H, d, J=8.6 Hz), 7.29-7.41 (5H, m), 7.75 (1H, dd, J=9.9, 0.8 Hz), 8.14 (1H, s), 8.25 (1H, d, J=2.1 Hz).

Workup

  1. extractionextracted with DCM
  2. customThe combined organics were dried
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by FCC
  5. customto give the impure product
  6. customThis residue was purified further by HPLC (XBridge C18 column, 35-98% MeCN in H2O, 0.1% NH4OH)
  7. customto give the product
  8. customThis residue purified further by HPLC (XBridge C18 column, 20-98% MeCN in H2O, 0.1% NH4OH)

Sources & evidence

ORD record
ord-e513c034fec74d6b910c4e615ef8dbee
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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