HCID 67959857, compound → HCID 86709784, compound

HRID 1529398Notes

Reaction equation

HRID 1529398 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([C:18]([F:21])([F:20])[F:19])=[CH2:17])=[CH:13][CH:14]=2)[C:9]([C:22]2[N:27]=[C:26]([O:28][C@H:29]3[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34][CH2:33][C:30]43[CH2:32][CH2:31]4)[CH:25]=[N:24][CH:23]=2)=[N:8]1>[Pd].C1COCC1>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([CH:16]([CH3:17])[C:18]([F:21])([F:19])[F:20])=[CH:13][CH:14]=2)[C:9]([C:22]2[N:27]=[C:26]([O:28][C@H:29]3[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])[CH2:34][CH2:33][C:30]43[CH2:32][CH2:31]4)[CH:25]=[N:24][CH:23]=2)=[N:8]1

Participants

4

Reactant 1

HCID 67959857HCID 67959857, compound

Product 1

HCID 86709784HCID 86709784, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A suspension of (4R)-tert-butyl 4-(6-(1-(tetrahydro-2H-pyran-2-yl)-5-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (100 mg, 0.167 mmol) and palladium on carbon (Aldrich, St. Louis, Mo.; 10% w/w; 17.75 mg, 0.017 mmol) in THF (2.0 mL) was cycled under a H2 atmosphere (1 atm; 3× evacuation/refill cycles) and stirred at 25° C. for 16 h. The mixture was filtered through Celite (washing with THF (3×5 mL) to quantitate the transfer) and the filtrate was concentrated in vacuo to provide (4R)-tert-butyl 4-(6-(1-(tetrahydro-2H-pyran-2-yl)-5-(1,1,1-trifluoropropan-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (100 mg, 0.166 mmol, 100% yield; mixture of epimers at C1) as a white foam: 1H NMR (400 MHz, CDCl3) δ ppm 9.03 (1 H, s), 8.39 (1 H, br. s.), 8.20 (1 H, br. s.), 7.64 (1 H, t, J=4.3 Hz), 7.36 (1 H, d, J=8.4 Hz), 5.81 (1 H, d, J=7.2 Hz), 4.66 (1 H, br. s.), 4.41 (1 H, br. s.), 4.28 (1 H, br. s.), 4.03 (1 H, d, J=11.3 Hz), 3.78 (1 H, br. s.), 3.57 (1H, quin, J=8.1 Hz), 3.23 (1 H, d, J=12.5 Hz), 2.95 (1 H, br. s.), 2.57-2.71 (1 H, m), 2.49 (1 H, br. s.), 2.17-2.25 (1 H, m), 2.13 (1 H, br. d, J=12.5 Hz), 1.80 (2 H, d, J=7.4 Hz), 1.71 (1 H, br. s.), 1.58 (3 H, dd, J=7.0, 3.1 Hz), 1.12 (9 H, br. s.), 0.85 (1 H, d, J=12.7 Hz), 0.70 (1 H, br. s.), 0.56-0.62 (1 H, m), 0.54 (2 H, br. s.). 19F NMR (377 MHz, CDCl3) δ ppm −71.44 (3 F, d, J=8.0 Hz). MS (ESI, pos. ion) m/z: 602.3 (M+1).

Workup

  1. filtrationThe mixture was filtered through Celite (
  2. washwashing with THF (3×5 mL)
  3. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-806b0acc0fc04442b235d3738fd382d9
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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