Tris(hydroxymethyl)aminomethane → HCID 178522523, compound

HRID 1452767Notes

Reaction equation

[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:15]3[S:14][C:13]([NH2:16])=[N:12][C:11]=3[NH:10][N:9]=2)=[CH:4][CH:3]=1.[CH:17]1([C:20](Cl)=[O:21])[CH2:19][CH2:18]1.C(O)C(N)(CO)CO>CN(C1C=CN=CC=1)C.C1COCC1>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:15]3[S:14][C:13]([NH:16][C:20]([CH:17]4[CH2:19][CH2:18]4)=[O:21])=[N:12][C:11]=3[NH:10][N:9]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a vial charged with 3-(4-hydroxyphenyl)-1H-pyrazolo[3,4-d]thiazol-5-ylamine (60 mg, 0.259 mmol), PS-DMAP (Argonaut resin, 1.05 g, 6 equiv.), and a stirring bar were added THF (2.5 mL) and cyclopropane-carbonyl chloride (118 μL, 1.29 mmol). The reaction mixture was stirred at 70° C. for 15 hours, then cooled to room temperature and treated with PS-trisamine (Argonaut resin, 1.26 g, 20 equiv.) at 50° C. for 48 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 32 mg (41% yield) of cyclopropanecarboxylic acid [3-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-d]thiazol-5-yl]-amide as a white solid. 1H-NMR (d6-DMSO) δ: 13.3 (broad s, 1H), 12.6 (broad s, 1H), 9.80 (broad s, 1H), 7.52 (d, 2H), 6.88 (d, 1H), 1.98 (m, 1H), 0.93 (m, 4H); HPLC/MS m/z: 301.0 [MH]+.

Workup

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

Sources & evidence

ORD record: ord-0977d82ae4534185a8a97cd18bccdba3
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473783B2

Reaction notes

Loading…