Tris(hydroxymethyl)aminomethane → HCID 178496261, compound

HRID 1452753Notes

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.[CH3:16][O:17][CH2:18][CH2:19][O:20][CH2:21][C:22](Cl)=[O:23].C(O)C(N)(CO)CO>CN(C1C=CN=CC=1)C.C1COCC1>[CH3:16][O:17][CH2:18][CH2:19][O:20][CH2:21][C:22]([NH:15][C:12]1[S:13][C:14]2[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:8][NH:9][C:10]=2[N:11]=1)=[O:23]

Participants

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, 6 equiv.), and a stirring bar was added THF (2 mL) and 2-(2-methoxyethoxy)acetyl chloride (106 μL, ca. 5 equiv.). The reaction mixture was stirred at 70° C. for 24 h, then cooled to room temperature and treated with PS-trisamine (Argonaut resin, 20 equiv.) for 1.5 h. The resin was filtered, washed with THF and the solvent was evaporated. The residue was treated with a (5:1:1) mixture of THF/H2O/Et3N (2 mL) at 50° C. for 24 h, then the solution was directly adsorbed on silica gel. Purification on silica gel with 0-10% MeOH in CH2Cl2 as eluent provided 30 mg (65%) of 2-(2-methoxy-ethoxy)-N-(3-phenyl-1H-pyrazolo[3,4-d]thiazol-5-yl)-acetamide as a white solid. 1H-NMR (d6-DMSO) δ: 13.5 and 13.6 (2 broad s, 1H, NH+tautomer), 12.2 (broad s, 1H, NH), 7.74 (m, 2H, tautomers), 7.54 (m, 2H, tautomers), 7.38 (m, 1H, tautomers), 4.28 (s, 2H), 3.68 (t, 2H), 3.51 (t, 2H), 3.29 (s, 3H); HPLC/MS m/z: 333 [MH]+.

Workup

temperaturecooled to room temperature
filtrationThe resin was filtered
washwashed with THF
customthe solvent was evaporated
additionThe residue was treated with a (5:1:1) mixture of THF/H2O/Et3N (2 mL) at 50° C. for 24 h
customPurification on silica gel with 0-10% MeOH in CH2Cl2 as eluent

Sources & evidence

ORD record: ord-c98033e98a22423c87877acb618a4a35
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473783B2

Reaction notes

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