Indole-3-acetamide → 2-(1H-Indol-3-yl)-N-(2-{2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophen-6-yl)-acetamide

HRID 1986297Notes

Reaction equation

HRID 1986297 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.[NH:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH2:37][C:38]([NH2:40])=[O:39])=[CH:29]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(#N)C>[NH:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH2:37][C:38]([NH:40][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)=[O:39])=[CH:29]1

Participants

7

Reactant 4

HCID 397Indole-3-acetamideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 68856615[4-(6-Bromobenzo[b]thiophen-2-yl)-pyrimidin-2-yl]-[3-(4-methylpiperazin-1-yl)-propyl]-amine

Product 1

HCID 577206122-(1H-Indol-3-yl)-N-(2-{2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophen-6-yl)-acetamideYield 26.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °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 (0.070 g, 0.16 mmol), 1.5 equivalent of 2-(1H-indol-3-yl)acetamide (0.041 g, 0.24 mmol), 4 mol % of tris(dibenzylideneacetone)dipalladium(0) (5.8 mg, 0.0063 mmol), 8 mol % of Xantphos (7.3 mg, 0.013 mmol), 1.5 equivalent of cesium carbonate (77 mg, 0.24 mmol) and acetonitrile (2 mL). The reaction is sealed and heated under microwave condition at 150° C. for 5 minutes, cooled down, filtered and then evaporated to furnish a red oil. This material is subjected to reverse phase purification, eluting with 20-95% CH3CN/0.01 M NH4HCO3 in water using a C18 Xterra column, to provide the title compound as a pale yellow solid (23 mg, 26% yield). ES+(m/z) 540 [M+H].

Workup

  1. customThe reaction is sealed
  2. temperaturecooled down
  3. filtrationfiltered
  4. customevaporated
  5. customto furnish a red oil
  6. customphase purification
  7. washeluting with 20-95% CH3CN/0.01 M NH4HCO3 in water using a C18 Xterra column

Sources & evidence

ORD record
ord-ef8e09967fa6442b8a6a08b9d5dda699
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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