Tris(hydroxymethyl)aminomethane → 5-morpholin-4-ylmethyl-furan-2-carboxylic acid [3-(2-bromo-phenyl)-1H-pyrazolo[3,4-d]thiazol-5-yl]-amide

HRID 1452765Notes

Reaction equation

HRID 1452765 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:15]2[S:14][C:13]([NH2:16])=[N:12][C:11]=2[NH:10][N:9]=1.Cl.[N:18]1([CH2:24][C:25]2[O:29][C:28]([C:30](Cl)=[O:31])=[CH:27][CH:26]=2)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(O)C(N)(CO)CO>CN(C1C=CN=CC=1)C.C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:15]2[S:14][C:13]([NH:16][C:30]([C:28]3[O:29][C:25]([CH2:24][N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)=[CH:26][CH:27]=3)=[O:31])=[N:12][C:11]=2[NH:10][N:9]=1

Participants

6

Reactant 3

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 866001495-Morpholin-4-ylmethyl-furan-2-carbonyl chloride hydrochlorideHCID 178508259HCID 178508259, compound

Product 1

HCID 1785225185-morpholin-4-ylmethyl-furan-2-carboxylic acid [3-(2-bromo-phenyl)-1H-pyrazolo[3,4-d]thiazol-5-yl]-amideYield 27.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a vial charged with 3-(2-bromo-phenyl)-1H-pyrazolo[3,4-d]thiazol-5-ylamine (30 mg, 0.135 mmol), PS-DMAP (Argonaut resin, 0.54 g, 6 equiv.), and a stirring bar was added THF (1.5 mL) and 5-morpholin-4-ylmethyl-furan-2-carbonyl chloride hydrochloride (180 mg, 0.675 mmol). The reaction mixture was stirred at 70° C. for 17 hours, then cooled to room temperature and treated with PS-trisamine (Argonaut resin, 0.76 g, 20 equiv.) at 50° C. for 8 hours. The resin was filtered, washed with DMF and the solvent was evaporated. Purification on silica gel with 0-8% MeOH in CH2Cl2 as eluent provided 18 mg (27% yield) of 5-morpholin-4-ylmethyl-furan-2-carboxylic acid [3-(2-bromo-phenyl)-1H-pyrazolo[3,4-d]thiazol-5-yl]-amide as a white solid. 1H-NMR (d6-DMSO) δ: 13.7 and 13.5 (2 broad s, 1H, NH+tautomer), 12.8 (broad s, 1H, NH), 7.65-7.82 (m, 3H), 7.49 and 7.55 (2 t, 1H, tautomers), 7.36 and 7.41 ( 2 t, 1H, tautomers), 6.58 (d, 1H), 3.59 (s, 2H), 3.56 (t, 4H), 2.41 (broad s, 4H); HPLC/MS m/z: 488.0, 490.0 [MH]+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe resin was filtered
  3. washwashed with DMF
  4. customthe solvent was evaporated
  5. customPurification on silica gel with 0-8% MeOH in CH2Cl2 as eluent

Sources & evidence

ORD record
ord-c3087bb4796041c49051d8af9cea3e17
Source dataset
uspto-grants-2009_01
Patent number
US07473783B2

Reaction notes

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