Diisopropylethylamine → HCID 58777647, compound

HRID 1435235Notes

Reaction equation

HRID 1435235 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[O:9])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[N:3]=1.C(N(C(C)C)CC)(C)C.[CH3:35][C:36]1[S:37][C:38]([CH3:45])=[CH:39][C:40]=1[S:41](Cl)(=[O:43])=[O:42]>O1CCCC1.C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[O:9])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:21][CH2:22][N:23]([S:41]([C:40]3[CH:39]=[C:38]([CH3:45])[S:37][C:36]=3[CH3:35])(=[O:43])=[O:42])[CH2:24][CH2:25]2)[N:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27796502,5-dimethylthiophene-3-sulfonyl ChlorideHCID 9997668[4-Amino-2-(piperidin-4-ylamino)-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone

Product 1

HCID 58777647HCID 58777647, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [4-amino-2-(piperidin-4-ylamino)-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone (50 mg, 0.145 mmol, Example 59) and diisopropylethylamine (Aldrich, 330 μL, 1.894 mmol) in anhydrous tetrahydrofuran (15 mL) cooled to 5° C., was added a solution of 2,5-dimethyl-3-thiophenesulfonyl chloride (Maybridge, 45.3 mg, 0.218 mmol) in methylene chloride (3 mL). The reaction mixture was stirred at room temperature overnight and then diluted with 50 mL of methylene chloride. The resulting solution was washed with saturated aqueous sodium bicarbonate (2×10 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 25% ethyl acetate in hexane yielded [4-amino-2-[1-(2,5-dimethyl-thiophene-3-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone (69 mg, 92%) as white solids. HR-MS (ES, m/z) calculated for C23H26FN5O4S2 [(M+H)+] 520.1483, observed 520.1494.

Workup

  1. washThe resulting solution was washed with saturated aqueous sodium bicarbonate (2×10 mL)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  5. washeluting with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d6fd71e1981f4b02819a86e405224e51
Source dataset
uspto-grants-2009_11
Patent number
US07615634B2

Reaction notes

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