Triethylamine → 2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-hydroxyacetic acid

HRID 1484970Notes

Reaction equation

HRID 1484970 reaction equation
[Si]([O:8][CH:9]([C:13]1[S:14][C:15]([C:18]2[N:23]=[C:22]([NH:24][C:25]3[CH:29]=[C:28]([CH:30]4[CH2:32][CH2:31]4)[NH:27][N:26]=3)[C:21]([Cl:33])=[CH:20][N:19]=2)=[CH:16][CH:17]=1)[C:10]([OH:12])=[O:11])(C(C)(C)C)(C)C.CCN(CC)CC>O1CCCC1.C(OCC)(=O)C>[Cl:33][C:21]1[C:22]([NH:24][C:25]2[CH:29]=[C:28]([CH:30]3[CH2:32][CH2:31]3)[NH:27][N:26]=2)=[N:23][C:18]([C:15]2[S:14][C:13]([CH:9]([OH:8])[C:10]([OH:12])=[O:11])=[CH:17][CH:16]=2)=[N:19][CH:20]=1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 581694892-(tert-butyldimethylsilyloxy)-2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino) pyrimidin-2-yl)thiophen-2-yl)acetic acid

Product 1

HCID 581691922-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-hydroxyacetic acidYield 64.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(tert-butyldimethylsilyloxy)-2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino) pyrimidin-2-yl)thiophen-2-yl)acetic acid (60 mg, 0.12 mmol, 1.0 equiv.) in tetrahydrofuran (10 mL) was added Et3N.3HF (0.06 mL, 0.36 mmol, 3.0 equiv.). The reaction mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate, washed (brine), dried (Na2SO4), filtered and concentrated to give a residue, the residue was purified by silica gel column chromatography (PE:EA=1:1) to afford 2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-hydroxyacetic acid (Compound 219) (30 mg, 64.6%). LC-MS (m/z): 392.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.75-0.76 (m, 2H), 0.97-0.99 (m, 2H), 1.92-1.96 (m, 1H), 5.31 (s, 1H), 6.45 (s, 1H), 7.13 (d, J=3.2 Hz, 1H), 7.67 (d, J=3.6 Hz, 1H), 8.39 (s, 1H), 9.30 (s, 1H), 12.59 (bs, 1H).

Workup

  1. washwashed (brine)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue
  6. customthe residue was purified by silica gel column chromatography (PE:EA=1:1)

Sources & evidence

ORD record
ord-31a6ef020b714fa681a06cb731ffea07
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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