Tetrabutylammonium Fluoride → 2-(4-{4-[7-amino-2-(isoquinolin-5-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanol

HRID 389505Notes

Reaction equation

HRID 389505 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH:21]=[C:20]([C:22]3[CH:27]=[N:26][C:25]([NH2:28])=[C:24]4[O:29][C:30]([C:32]5[CH:41]=[CH:40][CH:39]=[C:38]6[C:33]=5[CH:34]=[CH:35][N:36]=[CH:37]6)=[CH:31][C:23]=34)[CH:19]=[N:18]2)[CH2:13][CH2:12]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[NH2:28][C:25]1[N:26]=[CH:27][C:22]([C:20]2[CH:19]=[N:18][N:17]([CH:14]3[CH2:13][CH2:12][N:11]([CH2:10][CH2:9][OH:8])[CH2:16][CH2:15]3)[CH:21]=2)=[C:23]2[CH:31]=[C:30]([C:32]3[CH:41]=[CH:40][CH:39]=[C:38]4[C:33]=3[CH:34]=[CH:35][N:36]=[CH:37]4)[O:29][C:24]=12

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 66759523HCID 66759523, compound

Product 1

HCID 667605972-(4-{4-[7-amino-2-(isoquinolin-5-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanolYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-{1-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)piperidin-4-yl]-1H-pyrazol-4-yl}-2-(isoquinolin-5-yl)furo[2,3-c]pyridin-7-amine (60.8 mg, 0.112 mmol) was dissolved in THF (1.2 mL) and tetra-n-butylammonium fluoride (1.0 M in THF, 1.35 mL, 1.35 mmol) was added to the reaction. The reaction stirred 16 h at RT. The reaction was washed with sodium carbonate (2×), brine 2× and extracted with EtOAc (3×). The organic layers were collected, dried with sodium sulfate, filtered and then concentrated in vacuo to a solid. Purification by flash chromatography (0 to 15% NH3/MeOH:EtOAc) afforded 10.1 mg (34%) of the title compound. 1H NMR (400 MHz, CD3OD): δ 9.32 (s, 1 H), 8.54-8.58 (m, 1 H), 8.49 (d, J=6.32 Hz, 1 H), 8.34 (dd, J=7.33, 1.01 Hz, 2 H), 8.23 (d, J=8.08 Hz, 1 H), 8.13 (s, 1 H), 7.91 (d, J=7.07 Hz, 1 H), 7.81 (dd, J=8.08, 7.33 Hz, 1 H), 7.49 (s, 1 H), 4.18-4.32 (m, 1 H), 3.71 (t, J=6.06 Hz, 2 H), 3.14 (d, J=12.13 Hz, 2 H), 2.60 (t, J=6.06 Hz, 2 H), 2.25-2.36 (m, 2 H), 2.12-2.24 (m, 4 H); MS (ESI): 455.21 [M+H]+; HPLC tR=0.74 min (TOF: polar—3 min).

Workup

  1. washThe reaction was washed with sodium carbonate (2×), brine 2×
  2. extractionextracted with EtOAc (3×)
  3. customThe organic layers were collected
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to a solid
  7. customPurification by flash chromatography (0 to 15% NH3/MeOH:EtOAc)

Sources & evidence

ORD record
ord-91c8be57e7884bd5a7123c40bdb5ac3a
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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