Potassium Iodide → (2-(1H-indazol-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)-N-methyl,N-(3-morpholinopropylsulfonyl)methanamine

HRID 2262113Notes

Reaction equation

HRID 2262113 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:11]=[C:12]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[C:13]4[S:18][C:17]([CH2:19][N:20]([CH3:28])[S:21]([CH2:24][CH2:25][CH2:26]Cl)(=[O:23])=[O:22])=[CH:16][C:14]=4[N:15]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C>[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:11]=[C:12]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[C:13]4[S:18][C:17]([CH2:19][N:20]([CH3:28])[S:21]([CH2:24][CH2:25][CH2:26][N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)(=[O:23])=[O:22])=[CH:16][C:14]=4[N:15]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 8083MorpholineHCID 11430Potassium CarbonateHCID 671881163-chloro-propane-1-sulfonic acid [2-(1H-indazol-4-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]-methyl-amide

Product 1

HCID 59593044(2-(1H-indazol-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)-N-methyl,N-(3-morpholinopropylsulfonyl)methanamine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-chloro-propane-1-sulfonic acid [2-(1H-indazol-4-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]-methylamide (45 mg) in acetonitrile (2 mL) was added morpholine (38 μL), potassium carbonate (18 mg) and potassium iodide (2 mg). the reaction mixture was heated at 80° C. for 72 h and allowed to cool to room temperature before quenching with water (30 mL) and extracting into dichloromethane (2×30 mL). The combined organics were washed with brine (30 mL), dried (MgSO4), reduced in vacuo and purified by column chromatography to give 186 as an off-white solid (27 mg). NMR: CDCl3: 1.97 (m, 2H), 2.36-2.43 (m, 6H), 2.87 (s, 3H), 3.07 (m, 2H), 3.63 (t, J=4.6, 4H), 3.84 (t, J=4.8, 4H), 4.01 (t, J=4.8, 4H), 4.61 (s, 2H), 7.39 (s, 1H), 7.43 (t, J=8.2, 1H), 7.51 (d, J=8.3, 1H), 8.20 (d, J=6.8, 1H), 8.94 (s, 1H), 10.30 (brs, 1H). MS: ESI+: MH+ 572.09

Workup

  1. temperatureto cool to room temperature
  2. custombefore quenching with water (30 mL)
  3. extractionextracting into dichloromethane (2×30 mL)
  4. washThe combined organics were washed with brine (30 mL)
  5. dry with materialdried (MgSO4)
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-77d9afce95d840f2b1f6be23c054e0fb
Source dataset
uspto-grants-2010_12
Patent number
US07846929B2

Reaction notes

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