Tris(hydroxymethyl)aminomethane → N-{5-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-methylphenyl}-2-(2-thienyl)acetamide

HRID 1157633Notes

Reaction equation

HRID 1157633 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([CH3:24])=[C:21]([CH:23]=3)[NH2:22])=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[CH:25]1[CH:29]=[C:28]([CH2:30][C:31](Cl)=[O:32])[S:27][CH:26]=1.C(O)C(N)(CO)CO>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([CH3:24])=[C:21]([NH:22][C:31](=[O:32])[CH2:30][C:28]4[S:27][CH:26]=[CH:25][CH:29]=4)[CH:23]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 1623622-Thiopheneacetyl chlorideHCID 577372375-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-methylaniline

Product 1

HCID 57737250N-{5-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-methylphenyl}-2-(2-thienyl)acetamideYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-methylaniline (856 mg, 2.55 mmol) in THF (25 mL) was added thiophene-2-acetyl chloride (0.33 mL, 2.68 mmol). When TLC showed the reaction to be complete, PS-trisamine was added. After 16 h, TEA was added and the mixture was filtered. The filtrate was diluted with DCM and washed with water. The organic phase was dried over MgSO4 and concentrated onto silica gel. The crude material was purified by column chromatography to give of the desired product (1.13 g, 97%). 1H NMR (400 MHz, d6-DMSO) δ 9.63 (s, 1H), 8.87 (d, J=7.2 Hz, 1H), 8.43-8.39 (m, 2H), 7.70 (s, 1H), 7.62 (t, J=8.0 Hz, 1H), 7.38-7.30 (m, 3H), 7.20 (m, 1H), 7.18 (d, J=6.8 Hz, 1H), 7.09-6.95 (m, 2H), 3.91 (s, 2H), 2.28 (s, 3H) ppm.

Workup

  1. customthe reaction
  2. additionTEA was added
  3. filtrationthe mixture was filtered
  4. additionThe filtrate was diluted with DCM
  5. washwashed with water
  6. dry with materialThe organic phase was dried over MgSO4
  7. concentrationconcentrated onto silica gel
  8. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-a7ac30e56e9c4e3d85b705f00cd6415a
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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