Toluene → HCID 178432893, compound

HRID 1452755Notes

Reaction equation

HRID 1452755 reaction equation
[C:1]1([C:7]2[C:14]3[S:13][C:12]([NH2:15])=[N:11][C:10]=3[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:16][C:17]1[S:18][C:19]([C:23](Cl)=[O:24])=[C:20]([CH3:22])[N:21]=1.C1(C)C=CC=CC=1.C(O)C(N)(CO)CO>CN(C1C=CN=CC=1)C.C1COCC1>[C:1]1([C:7]2[C:14]3[S:13][C:12]([NH:15][C:23]([C:19]4[S:18][C:17]([Cl:16])=[N:21][C:20]=4[CH3:22])=[O:24])=[N:11][C:10]=3[NH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 6503Tris(hydroxymethyl)aminomethaneHCID 135933932-Chloro-4-methylthiazole-5-carboxylic acid chlorideHCID 178508260HCID 178508260, compound

Product 1

HCID 178432893HCID 178432893, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a vial charged with 3-phenyl-1H-pyrazolo[3,4-d]thiazol-5-ylamine (30 mg, 0.139 mmol), PS-DMAP (Argonaut resin, 558 mg, 6 equiv.), and a stirring bar was added THF (2 mL) and 2-chloro-4-methyl-thiazole-5-carbonyl chloride solution in toluene (0.52 M, 1.3 mL, ca. 5 equiv.). The reaction mixture was stirred at 70° C. for 18 hours, then cooled to room temperature and treated with PS-trisamine (Argonaut resin, 674 mg, 20 equiv.) for 2 hours. The resin was filtered, washed with THF and the solvent was evaporated. The resulting crude mixture was treated with MeOH (1 mL) and a 4 N aqueous solution of NaOH (0.25 mL). The reaction mixture was further stirred at room temperature for 2 hours, then a 1 N aqueous solution of HCl was added to adjust the pH to 7, and the mixture was extracted with EtOAc (3×). Purification on silica gel with 0-10% MeOH in CH2Cl2 as eluent provided 11 mg (21% yield) of 2-chloro-4-methyl-thiazole-5-carboxylic acid (3-phenyl-1H-pyrazolo[3,4-d]thiazol-5-yl)-amide as an off-white solid. 1H-NMR (d6-DMSO) δ: 7.75 (d, 2H), 7.54 (t, 2H), 7.39 (t, 1H), 2.65 (s, 3H); HPLC/MS m/z: 376.0 [MH]+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe resin was filtered
  3. washwashed with THF
  4. customthe solvent was evaporated
  5. additionThe resulting crude mixture was treated with MeOH (1 mL)
  6. stirringThe reaction mixture was further stirred at room temperature for 2 hours
  7. additiona 1 N aqueous solution of HCl was added
  8. extractionthe mixture was extracted with EtOAc (3×)
  9. customPurification on silica gel with 0-10% MeOH in CH2Cl2 as eluent

Sources & evidence

ORD record
ord-0f65f635efb84ec7ba99956cb4bace99
Source dataset
uspto-grants-2009_01
Patent number
US07473783B2

Reaction notes

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