Pyridine → HCID 178441967, compound

HRID 1452752Notes

Reaction equation

HRID 1452752 reaction equation
[C:1]([C:5]1[C:12]2[S:11][C:10]([NH2:13])=[N:9][C:8]=2[NH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[O:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[C:25](Cl)=[O:26].C(O)C(N)(CO)CO>CN(C1C=CN=CC=1)C.C1COCC1>[C:1]([C:5]1[C:12]2[S:11][C:10]([NH:13][C:25]([C:21]3[O:20][CH:24]=[CH:23][CH:22]=3)=[O:26])=[N:9][C:8]=2[NH:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 1049PyridineHCID 6503Tris(hydroxymethyl)aminomethaneHCID 682422-Furancarbonyl chlorideHCID 178441968HCID 178441968, compound

Product 1

HCID 178441967HCID 178441967, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

To a stirring solution of 3-tert-Butyl-1H-pyrazolo[3,4-d]thiazol-5-ylamine (30 mg, 0.153 mmol) and pyridine (74 μL, 0.92 mmol), or alternatively PS-DMAP (Argonaut resin, 6 equiv.), in THF (0.75 mL) was added furan-2-carbonyl chloride (75 μL, 0.76 mmol). The reaction mixture was stirred at 70° C. for 23 h, then cooled to room temperature and treated with THF (1 mL) and PS-trisamine (Argonaut resin, 20 equiv.) for 2 h. The resin was filtered, washed with DMF and the solvent was evaporated. The residue was treated with MeOH (1 mL) and a 4N aqueous solution of NaOH (0.25 mL) and the solution was stirred at room temperature for 2 h. The reaction mixture was neutralized to pH 7 with a 1N aqueous solution of HCl and extracted with ethyl acetate (3×). Purification on silica gel with 0-10% MeOH in CH2Cl2 as eluent provided 36 mg (82%) of furan-2-carboxylic acid (3-tert-butyl-1H-pyrazolo[3,4-d]thiazol-5-yl)-amide as an off-white solid. 1H-NMR (d6-DMSO) δ: 12.8 (broad s, 1H, NH), 12.7 (broad s, 1H, NH), 8.03 (d, 1H), 7.69 (broad s, 1H), 6.74 (dd, 1H), 1.36 (s, 9H); HPLC/MS m/z: 291 [MH]+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe resin was filtered
  3. washwashed with DMF
  4. customthe solvent was evaporated
  5. additionThe residue was treated with MeOH (1 mL)
  6. stirringa 4N aqueous solution of NaOH (0.25 mL) and the solution was stirred at room temperature for 2 h
  7. extractionextracted with ethyl acetate (3×)
  8. customPurification on silica gel with 0-10% MeOH in CH2Cl2 as eluent

Sources & evidence

ORD record
ord-04122794be3f41ac8969b9a1195c607b
Source dataset
uspto-grants-2009_01
Patent number
US07473783B2

Reaction notes

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