Ammonium Hydroxide → HCID 86667474, compound

HRID 2401788Notes

Reaction equation

HRID 2401788 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([Cl:21])[CH:16]=3)[S:10][C:11]=2[C:12](O)=[O:13])=[CH:4][CH:3]=1.CC[N:26]=C=NCCCN(C)C.O.ON1C2C=CC=CC=2N=N1.[OH-].[NH4+]>C(Cl)Cl.O>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([Cl:21])[CH:16]=3)[S:10][C:11]=2[C:12]([NH2:26])=[O:13])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 14923Ammonium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86667472HCID 86667472, compound

Product 1

HCID 86667474HCID 86667474, compoundYield 67.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-(4-chlorobenzyl)-2-(2-chloropyridin-4-yl)thiazole-5-carboxylic acid (179 mg, 0.490 mmol) in DCM (27.5 mL) was added EDCI (282 mg, 1.47 mmol) and 1-hydroxybenzotriazole hydrate (150 mg, 0.980 mmol) and the solution was stirred for 10 minutes. 28% ammonium hydroxide (2.12 mL, 24.5 mmol) was added and the resulting mixture was stirred at room temperature overnight. Water (20 mL) was added and the mixture was extracted with DCM (2×25 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (methanol/DCM=0/100→15/85) to give 121 mg of the title compound as a white solid (67% yield). LC/MS (FA) ES+ 364, 366. 1H NMR (400 MHz, d6-DMSO) δ: 8.54 (dd, 1H, J=5.2, 0.7 Hz), 8.02 (bs, 1H), 7.91 (dd, 1H, J=1.5, 0.7 Hz), 7.84 (dd, 1H, J=5.2, 1.5 Hz), 7.79 (bs, 1H), 7.36-7.29 (m, 4H), 4.43 (s, 2H).

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with DCM (2×25 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (methanol/DCM=0/100→15/85)

Sources & evidence

ORD record
ord-7ea5b8604ab042608421c53b3a90066f
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

Loading…