Potassium Carbonate → HCID 178470646, compound

HRID 1526492Notes

Reaction equation

HRID 1526492 reaction equation
Cl[C:2]1[C:3]2[C:4]3[C:9]([S:10][C:11]=2[N:12]=[CH:13][N:14]=1)=[CH:8][CH:7]=[C:6]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:5]=3.C(=O)([O-])[O-].[K+].[K+].[N:27]1([C@H:33]2[CH2:38][CH2:37][C@H:36]([NH2:39])[CH2:35][CH2:34]2)[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>CC#N>[O:30]1[CH2:29][CH2:28][N:27]([C@H:33]2[CH2:34][CH2:35][C@H:36]([NH:39][C:2]3[C:3]4[C:4]5[CH:5]=[C:6]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:7]=[CH:8][C:9]=5[S:10][C:11]=4[N:12]=[CH:13][N:14]=3)[CH2:37][CH2:38]2)[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86707952HCID 86707952, compoundHCID 178511580HCID 178511580, compound

Product 1

HCID 178470646HCID 178470646, compoundYield 40.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A solution of ethyl 2-[3-chloro-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(13),2(7),3,5,9,11-hexaen-12-yl]acetate (500 mg, 1.63 mmol, 1.00 equiv) in MeCN (100 mL) was added potassium carbonate (2.2 g, 15.92 mmol, 10.00 equiv), TEA (495 mg, 4.89 mmol, 3.00 equiv) and trans-4-(morpholin-4-yl)cyclohexan-1-amine (1.5 g, 8.14 mmol, 5.00 equiv) subsequently at room temperature under nitrogen. The resulting solution was stirred overnight at 80° C. and cooled down to r.t. The reaction was quenched with water, extracted with 3×100 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by silica gel column chromatography with dichloromethane/methanol (20/1) to give 300 mg (40%) of the corresponding ethyl 2-(4-(((trans)-4-morpholinocyclohexyl)amino)benzo[4,5]thieno[2,3-d]pyrimidin-6-yl)acetate as an off-white solid. LCMS: (ES, m/z) 455 (M+H+). 1H-NMR (300 MHz, CDCl3) δ 8.57 (s, 1H), 7.88-7.85 (d, 1H), 7.71 (s, 1H), 7.42-7.40 (d, 1H), 5.33-5.31 (d, 1H), 4.30-4.21 (m, 1H), 4.19-4.09 (q, 2H), 3.81 (s, 2H), 3.75 (s, 4H), 2.61 (s, 4H), 2.38 (s, 3H), 2.05 (s, 2H), 1.55-1.52 (d, 2H), 1.45-1.41 (m, 2H), 1.31-1.27 (t, 3H).

Workup

  1. temperaturecooled down to r.t
  2. customThe reaction was quenched with water
  3. extractionextracted with 3×100 mL of ethyl acetate
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by silica gel column chromatography with dichloromethane/methanol (20/1)

Sources & evidence

ORD record
ord-ab8fae9a6b834c9490f8b86f558b3d06
Source dataset
uspto-grants-2015_07
Patent number
US09085586B2

Reaction notes

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