HCID 57506731, compound → HCID 49834222, compound

HRID 1922938Notes

Reaction equation

HRID 1922938 reaction equation
[N:1]1([C:7]2[C:8]3[S:28][C:27]([CH2:29][N:30]4[CH2:33][CH:32]([N:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)[CH2:31]4)=[CH:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C1(S([N:49]2[C:57]3[CH:56]=[CH:55][N:54]=[C:53](Br)[C:52]=3[CH:51]=[CH:50]2)(=O)=O)C=CC=CC=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.S1C=CC=C1C([O-])=O.[Cu+]>[O:4]1[CH2:3][CH2:2][N:1]([C:7]2[C:8]3[S:28][C:27]([CH2:29][N:30]4[CH2:31][CH:32]([N:34]5[CH2:35][CH2:36][O:37][CH2:38][CH2:39]5)[CH2:33]4)=[CH:26][C:9]=3[N:10]=[C:11]([C:53]3[C:52]4[CH:51]=[CH:50][NH:49][C:57]=4[CH:56]=[CH:55][N:54]=3)[N:12]=2)[CH2:6][CH2:5]1

Participants

6

Reactant 2

HCID 57506731HCID 57506731, compoundHCID 59606055HCID 59606055, compound

Product 1

HCID 49834222HCID 49834222, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)-2-(tributylstannanyl)thieno[3,2-d]pyrimidine (192 mg, 0.29 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (117 mg, 0.35 mmol), tetrakis(triphenylphosphine)palladium (34 mg, 10 mol %) and copper(I)-thiophene-2-carboxylate (11 mg, 20 mol %) in dioxane (2.0 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH/DCM then eluted with 2 M NH3 in MeOH. The resulting residue was dissolved in IMS/dioxane (1:1 mL) and 12.5 M aqueous NaOH solution (0.1 mL) added. After stirring for 1 h the reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH/DCM then eluted with 2 M NH3 in MeOH/DCM. The resulting residue was purified by column chromatography (Si—PCC, 2 M NH3 in MeOH:DCM, gradient 0:100 to 10:90) followed by trituration from diethyl ether to give 174 (38 mg, 27%) as a pale yellow solid. LCMS RT 4.52 min, [M+H]+ 492. 1H NMR (CDCl3, 400 MHz) δ 8.53 (m, 1 H), 7.45-7.35 (m, 4 H), 4.10 (t, J=4.7 Hz, 4 H), 3.97 (s, 2 H), 3.89 (t, J=4.7 Hz, 4 H), 3.72 (t, J=4.5 Hz, 4 H), 3.69-3.54 (m, 2 H), 3.08-3.01 (m, 3H), 2.33 (m, 4 H).

Workup

  1. customwas purged with argon gas
  2. washwashed with MeOH/DCM
  3. washthen eluted with 2 M NH3 in MeOH
  4. dissolutionThe resulting residue was dissolved in IMS/dioxane (1:1 mL)
  5. addition12.5 M aqueous NaOH solution (0.1 mL) added
  6. washwashed with MeOH/DCM
  7. washthen eluted with 2 M NH3 in MeOH/DCM
  8. customThe resulting residue was purified by column chromatography (Si—PCC, 2 M NH3 in MeOH:DCM, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-007f75035cd5440a8656c8f6544d738d
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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