Sodium Bicarbonate → N-Methyl-3-(2-{2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophen-6-yl)-benzamide

HRID 1986299Notes

Reaction equation

HRID 1986299 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH:16][CH2:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)[N:11]=3)[S:7][C:6]=2[CH:27]=1.[CH3:28][NH:29][C:30]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)=[O:31].C([O-])(O)=O.[Na+]>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.CS(C)=O.O>[CH3:28][NH:29][C:30](=[O:31])[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:2]2[CH:3]=[CH:4][C:5]3[CH:9]=[C:8]([C:10]4[CH:15]=[CH:14][N:13]=[C:12]([NH:16][CH2:17][CH2:18][CH2:19][N:20]5[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]5)[N:11]=4)[S:7][C:6]=3[CH:27]=2)[CH:33]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27735243-(Methylcarbamoyl)benzeneboronic acidHCID 68856615[4-(6-Bromobenzo[b]thiophen-2-yl)-pyrimidin-2-yl]-[3-(4-methylpiperazin-1-yl)-propyl]-amine

Product 1

HCID 68857904N-Methyl-3-(2-{2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophen-6-yl)-benzamideYield 40%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 23503278(Methanesulfinyl)methane--water (1/1)Solvent

Conditions

Temperature
170 °C

Procedure

A microwave tube is charged with [4-(6-bromobenzo[b]thiophen-2-yl)-pyrimidin-2-yl]-[3-(4-methylpiperazin-1-yl)-propyl]-amine (41 mg, 0.092 mmol), 1.6 equivalent of 3-(methylcarbamoyl)phenylboronic acid (27 mg, 0.15 mmol), 5 mol % of tetrakis(triphenylphosphine)palladium(0) (5.0 mg, 0.0046 mmol), 1.2 equivalent of NaHCO3 (10 mg, 0.11 mmol) and 2:1 DMSO/H2O solution (3 mL). The reaction is sealed and heated under microwave condition at 170° C. for 20 minutes, cooled down, filtered through SCX column and washed several time with dichloromethane/MeOH (1:1). The product is then released with 0.1 M NH3 solution in MeOH, collected and evaporated to give a brown oil. The oil is subjected to reverse phase purification, eluting with 5-95% CH3CN/0.01 N NH4HCO3 in water using a C18 Xterra column, to give the title compound as a pale yellow solid (10 mg, 40% yield). ES+(m/z) 501 [M+H].

Workup

  1. customThe reaction is sealed
  2. temperaturecooled down
  3. filtrationfiltered through SCX column
  4. washwashed several time with dichloromethane/MeOH (1:1)
  5. customcollected
  6. customevaporated
  7. customto give a brown oil
  8. customphase purification
  9. washeluting with 5-95% CH3CN/0.01 N NH4HCO3 in water using a C18 Xterra column

Sources & evidence

ORD record
ord-bd73d73ad44746f7b388a75461792a42
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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