Acetic Acid → HCID 58203918, compound

HRID 2386003Notes

Reaction equation

HRID 2386003 reaction equation
[F:1][C:2]([F:32])([F:31])[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]([CH2:28][CH:29]=O)[CH:27]=5)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1.[CH2:33]([NH:35][CH2:36][CH3:37])[CH3:34].C(O)(=O)C.C([BH3-])#N.[Na+]>C(Cl)Cl>[CH2:33]([N:35]([CH2:36][CH3:37])[CH2:29][CH2:28][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:31])([F:32])[F:1])[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)[CH3:34]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8021DiethylamineHCID 5003444Sodium cyanoborohydrideHCID 86652329HCID 86652329, compound

Product 1

HCID 58203918HCID 58203918, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a reaction vial charged with 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)-ethanol 150 (0.250 g, 0.540 mmol) was added 4 mL DCM to give a slurry. Next, Dess-Martin periodinane (1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one, 0.2522 g, 0.594 mmol) was added portion-wise and the reaction mixture was stirred at room temperature with LCMS monitor. Full conversion was seen after 30 minutes reaction time. The reaction mixture was diluted with water to give a white precipitate. This solid was collected by vacuum filtration, washed with EtOAc and dried on high vacuum to give the intermediate aldehyde, 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)-ethanal. To a suspension of the aldehyde (0.160 g, 0.347 mmol) and diethylamine (0.127 g, 1.74 mmol) in 1.0 ml of DCM was added acetic acid (0.0198 mL, 0.347 mmol) and the reaction mixture was heated at 40 C for 1 hour. Finally sodium cyanoborohydride (0.0350 g, 0.556 mmol) was added in portions. The reaction mixture was heated at 40° C. for 45 minutes with complete conversion to product as determined by LCMS. The cooled reaction mixture was diluted with DCM, washed with water and saline, and concentrated to a solid which was purified by RP-HPLC to give 484. MS: (ESI+)=518.2

Workup

  1. temperaturethe reaction mixture was heated at 40 C for 1 hour
  2. customThe cooled reaction mixture
  3. washwashed with water and saline
  4. concentrationconcentrated to a solid which
  5. customwas purified by RP-HPLC

Sources & evidence

ORD record
ord-82e9934b1782458f85d43c06cbe8a944
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

Loading…