Tetrahydrofuran → 2-methyl-2-(4-{2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl}-pyrazol-1-yl)-propylamine

HRID 2385926Notes

Reaction equation

HRID 2385926 reaction equation
[F:1][C:2]([F:35])([F:34])[CH2:3][N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([C:23]5[CH:24]=[N:25][N:26]([C:28]([CH3:33])([CH3:32])[C:29]([NH2:31])=O)[CH:27]=5)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1.O1CCCC1.[AlH4-].[Li+]>>[CH3:33][C:28]([N:26]1[CH:27]=[C:23]([C:21]2[CH:20]=[CH:19][C:16]3[C:17]4[N:18]=[C:9]([C:8]5[N:4]([CH2:3][C:2]([F:1])([F:35])[F:34])[N:5]=[CH:6][N:7]=5)[S:10][C:11]=4[CH2:12][CH2:13][O:14][C:15]=3[CH:22]=2)[CH:24]=[N:25]1)([CH3:32])[CH2:29][NH2:31]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 28112Lithium aluminum hydrideHCID 670617512-(4-{2-[2-(2,2,2-Trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl}-pyrazol-1-yl)-isobutyramide

Product 1

HCID 582042072-methyl-2-(4-{2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl}-pyrazol-1-yl)-propylamineYield 7.2%

Procedure

To a solution of 2-(4-{2-[2-(2,2,2-Trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl}-pyrazol-1-yl)-isobutyramide (0.182 g, 0.000361 mol) in tetrahydrofuran (5.864 mL, 0.07229 mol) under N2 at 0° C. was added lithium tetrahydroaluminate (1M in THF, 1.44 mL, 0.00145 mol) dropwise. The reaction was stirred at room temperature for 6 h. The reaction was quenched with saturated Na2SO4 until no more hydrogen evolution was observed. MgSO4 was added and the solution was filtered and rinsed with copious amounts of methylene chloride. The mixture was concentrated and purified by reverse-phase HPLC to give 412 (12.8 mg) as a colorless solid. MS (ESI+) 490.1. 1H NMR (400 MHz, DMSO) δ 8.36 (s, 1H), 8.29 (s, 1H), 8.26 (d, J=8.3, 1H), 7.98 (s, 1H), 7.49 (dd, J=8.3, 1.7, 1H), 7.37 (d, J=1.7, 1H), 5.86 (q, J=8.7, 2H), 4.39 (t, J=5.0, 2H), 3.47 (t, J=5.0, 2H), 2.86 (s, 2H), 1.50 (s, 6H)

Workup

  1. customThe reaction was quenched with saturated Na2SO4 until no more hydrogen evolution
  2. additionMgSO4 was added
  3. filtrationthe solution was filtered
  4. washrinsed with copious amounts of methylene chloride
  5. concentrationThe mixture was concentrated
  6. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-76c41147f3124c4a87efacbec8647c9c
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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