2-Methylpropan-2-olate → 1-{2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulen-9-yl}-piperidin-4-ol

HRID 707879Notes

Reaction equation

HRID 707879 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:16]([C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=5[F:27])[N:17]=[CH:18][N:19]=4)[S:8][C:7]=3[C:6]=2[N:28]=1.C[Si](C)(C)[O:31][CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(N1CCN2CCN(CCCC)P1N(CCCC)CC2)CCC.CC(C)([O-])C>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[N:16]1[C:15]([C:9]2[S:8][C:7]3[C:6]4[N:28]=[C:2]([N:35]5[CH2:36][CH2:37][CH:32]([OH:31])[CH2:33][CH2:34]5)[CH:3]=[CH:4][C:5]=4[O:14][CH2:13][CH2:12][C:11]=3[CH:10]=2)=[N:19][CH:18]=[N:17]1

Participants

7

Reactant 4

HCID 45749132-Methylpropan-2-olateHCID 178325924-Tri-methylsilanyloxy-piperidineHCID 575886892,8,9-Tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecaneHCID 579003099-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene

Product 1

HCID 582038291-{2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulen-9-yl}-piperidin-4-olYield 38%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (300 mg, 0.72 mmol), Pd(OAc)2 (49 mg, 0.3 mmol), 4-Tri-methylsilanyloxy-piperidine (186 mg, 1.44 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (140 mg, 1.44 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 120° C. for 6 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-HPLC to afford 130 mg of 124 (yield=38%). 1H NMR (MeOD, 400 MHz): δ8.11 (s, 1H), 7.68-7.66 (m, 1H), 7.33-7.23 (m, 3H), 7.10-7.08 (m, 1H), 6.54-6.52 (m, 1H), 4.16-4.13 (m, 2H), 3.90-3.86 (m, 2H), 3.76-3.72 (m, 2H), 3.07-3.04 (m, 2H), 2.95-2.89 (m, 2H), 1.86-1.82 (m, 2H), 1.44-1.41 (m, 2H). LC-MS (ESI): m/z=482 [M+H]+

Workup

  1. customwas bubbled N2 for 10 min
  2. filtrationThe mixture was filtered over ceilite
  3. concentrationThe filtrate was concentrated to dryness
  4. custompurified by pre-HPLC

Sources & evidence

ORD record
ord-7e0ffc3b4802434f96fe2cc954799207
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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