Potassium Hydroxide → HCID 51348058, compound

HRID 1629433Notes

Reaction equation

HRID 1629433 reaction equation
[Cl:1][C:2]1[N:28]=[CH:27][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH2:22][C:23]([F:26])([F:25])[F:24])[N:16]=[C:17]([CH2:19][O:20]C)[N:18]=1)[N:7]=3.[OH-].[K+]>Br>[Cl:1][C:2]1[N:28]=[CH:27][C:5]2[C:6]3[N:10]([CH:9]=[C:8]([C:14]4[N:15]([CH2:22][C:23]([F:26])([F:25])[F:24])[N:16]=[C:17]([CH2:19][OH:20])[N:18]=4)[N:7]=3)[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 86652309HCID 86652309, compound

Product 1

HCID 51348058HCID 51348058, compoundYield 3.5%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 8-Chloro-2-[5-methoxymethyl-2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene (500 mg, 1.20 mmol) in 48% aqueous HBr (2.1 mL) was sealed and heated at 100° C. for 3 h while carefully monitoring by LCMS. The mixture was cooled to room temperature and poured over a cold solution of 10% KOH. The solid was collect by filtration (˜90% purity by LCMS and 1H NMR analysis). The solid was used in subsequent steps without purification. A small amount was purified by HPLC to give 17 mg of 387. LCMS: 401.0. 1H NMR (400 MHz, DMSO) δ 9.27 (s, 1H), 8.11 (s, 1H), 7.24 (s, 1H), 5.81 (q, J=8.9 Hz, 2H), 5.34 (t, J=6.0 Hz, 1H), 4.71-4.57 (m, 4H), 4.46 (d, J=6.0 Hz, 2H).

Workup

  1. customwas sealed
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationThe solid was collect by filtration (˜90% purity by LCMS and 1H NMR analysis)
  4. customThe solid was used in subsequent steps without purification
  5. customA small amount was purified by HPLC

Sources & evidence

ORD record
ord-ed3faa5345e5463c83035bd54fc2061c
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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