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

HRID 1484966Notes

Reaction equation

HRID 1484966 reaction equation
[Si]([O:8][CH:9]([C:15]1[S:16][C:17]([C:20]2[N:25]=[C:24]([NH:26][C:27]3[CH:31]=[C:30]([CH:32]4[CH2:34][CH2:33]4)[NH:29][N:28]=3)[C:23]([Cl:35])=[CH:22][N:21]=2)=[CH:18][CH:19]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11])(C(C)(C)C)(C)C.CCN(CC)CC>O1CCCC1.C(OCC)(=O)C>[Cl:35][C:23]1[C:24]([NH:26][C:27]2[CH:31]=[C:30]([CH:32]3[CH2:34][CH2:33]3)[NH:29][N:28]=2)=[N:25][C:20]([C:17]2[S:16][C:15]([CH:9]([OH:8])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:19][CH:18]=2)=[N:21][CH:22]=1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 58169434ethyl 2-(tert-butyldimethylsilyloxy)-2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)acetate

Product 1

HCID 58169421Ethyl 2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-hydroxyacetateYield 79.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 2-(tert-butyldimethylsilyloxy)-2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)acetate (200 mg, 0.37 mmol, 1.0 eq) in tetrahydrofuran (10 mL) was added Et3N.3HF (0.2 mL, 1.11 mmol, 3.0 eq). 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, which was purified by silica gel column chromatography (PE:EA=1:1) to give Ethyl 2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-hydroxyacetate (Compound 191) (123 mg, 78.6%). LC-MS (m/z): 420.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.73-0.77 (m, 2H), 0.96-1.01 (m, 2H), 1.21 (t, J=7.0 Hz, 3H), 1.91-1.98 (m, 1H), 4.14-4.19 (m, 2H), 5.42 (d, J=4.8 Hz, 1H), 6.44 (s, 1H), 6.52 (d, J=5.6 Hz, 1H), 7.13 (d, J=4.0 Hz, 1H), 7.67 (d, J=4.0 Hz, 1H), 8.40 (s, 1H), 9.29 (s, 1H), 12.30 (bs, 1H).

Workup

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

Sources & evidence

ORD record
ord-382ecc273ea1452ab34ab02a7fb94ede
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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