Ammonium Chloride → HCID 18537395, compound

HRID 412962Notes

Reaction equation

HRID 412962 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:10]2[N:11]=[C:12]([C:15]3[CH:16]=[C:17]([C:22]([NH2:24])=[NH:23])[S:18][C:19]=3[S:20][CH3:21])[S:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].C(OC1C=C(C2N=C(C3C=C(C(OC)=O)SC=3SC)SC=2)C=CC=1OC)(=O)C.[Cl-:53].[NH4+].C[Al](C)C>C1(C)C=CC=CC=1.CN(C=O)C.CO.C(Cl)Cl>[ClH:53].[OH:1][C:2]1[CH:3]=[C:4]([C:10]2[N:11]=[C:12]([C:15]3[CH:16]=[C:17]([C:22]([NH2:24])=[NH:23])[S:18][C:19]=3[S:20][CH3:21])[S:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 16682925TrimethylaluminumHCID 18536857HCID 18536857, compoundHCID 18537416HCID 18537416, compound

Product 1

HCID 18537395HCID 18537395, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

4-[4-(3-Hydroxy-4-methoxyphenyl)(1,3-thiazol-2-yl)]-5-methylthiothiophene-2-carboxamidine hydrochiloride: A portion of the mixture (320 mg, ca. 0.788 mmol as based on the 1H-NMR spectrum) containing the 2-methoxy-5-{2-[5-(methoxvcarbonyl)-2-methylthio(3-thienyl)](1,3-thiazol-4-yl)}phenyl acetate (as prepared in the previous step) was treated according to the procedure in Example 10, step (b), using 415 mg (7.76 mmol) of ammonium chloride in 3.5 mL of toluene and 3.88 mL (7.66 mmol) of 2 M trimethylaluminum in toluene. After chromatography of the resulting residue on a 10 g silica SPE column (Waters Sep-Pak) with 10-40% MeOH-CH2Cl2, a light yellow solid was obtained which was dissolved in 45 mL of DMF and filtered to remove silica gel. Concentration under high vacuum and recrystallization from MeOH—Et2O afforded the title compound as a light tan solid (132 mg, 44%). 1H-NMR (300 MHz, DMSO-d6) δ 9.49 (broad s, 2H), 9.16 (broad s, 2H), 8.67 (s, 1H), 7.98 (s, 1H), 7.5 (obscured m, 3H), 7.00 (obscured d, 1H, J=8.3 Hz), 3.82 (s, 3H), and 2.79 (s, 3H). Mass spectrum (ESI) calcd. for C16H15N3O2S3: 378.0 (M+H). Found: 378.1.

Workup

  1. customas prepared in the previous step)
  2. additionwas treated
  3. filtrationfiltered
  4. customto remove silica gel
  5. concentrationConcentration
  6. customunder high vacuum and recrystallization from MeOH—Et2O

Sources & evidence

ORD record
ord-b225de112ae34addab584105b1e950a5
Source dataset
uspto-grants-2003_05
Patent number
US06562840B1

Reaction notes

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