Tris(hydroxymethyl)aminomethane → HCID 178476623, compound

HRID 1452771Notes

Reaction equation

HRID 1452771 reaction equation
[Cl: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.[C:17]([O:20][C@@H:21]([CH3:25])[C:22](Cl)=[O:23])(=[O:19])[CH3:18].C(O)C(N)(CO)CO>CN(C1C=CN=CC=1)C.C1COCC1>[Cl: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:22]([C@@H:21]([O:20][C:17](=[O:19])[CH3:18])[CH3:25])=[O:23])=[N:12][C:11]=2[NH:10][N:9]=1

Participants

6

Reactant 3

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 178508261HCID 178508261, compound

Product 1

HCID 178476623HCID 178476623, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a vial charged with 3-(2-chloro-phenyl)-1H-pyrazolo[3,4-d]thiazol-5-ylamine (30 mg, 0.12 mmol) and PS-DMAP (Argonaut resin, 450 mg, 5 equiv.) were added THF (0.8 mL) and (S)-(−)-2-acetoxypropionyl chloride (126 mg, 0.84 mmol). The reaction mixture was shaken at 70° C. overnight, then cooled to room temperature and treated with PS-trisamine (Argonaut resin, 1.03 g, 30 equiv.) at 50° C. for 4 hours. The resin was filtered, washed with DMF and the solvent was evaporated. Purification by reverse-phase preparative HPLC provided 21 mg (48% yield) of the title compound. 1H-NMR (d6-DMSO) δ: 7.78 (broad m, 1H), 7.61 (broad m, 1H), 7.47 (broad m, 2H), 5.13 (q, 1H), 2.09 (s, 3H), 1.44 (d, 3H); HPLC/MS m/z: 365.0 [MH]+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe resin was filtered
  3. washwashed with DMF
  4. customthe solvent was evaporated
  5. customPurification by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-5f45a7c8551941d3b30ca11df6313e79
Source dataset
uspto-grants-2009_01
Patent number
US07473783B2

Reaction notes

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