Potassium Phosphate, Tribasic → 5-bromo-N-(1-cyclohexyl-5-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-amine

HRID 2068300Notes

Reaction equation

HRID 2068300 reaction equation
[CH:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([CH2:16][N:17]4[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]4)=[CH:15][C:10]=3[N:9]=[C:8]2[NH2:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[N:29]=[C:28]2I.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.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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]>[Br:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[N:29]=[C:28]2[NH:23][C:8]1[N:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[C:11]2[CH:12]=[CH:13][C:14]([CH2:16][N:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)=[CH:15][C:10]=2[N:9]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 218991781-Cyclohexyl-5-[(piperidin-1-yl)methyl]-1H-benzimidazol-2-amineHCID 583172565-Bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole

Product 1

HCID 672544035-bromo-N-(1-cyclohexyl-5-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-amineYield 68.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1-cyclohexyl-5-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2-amine (420 mg, 0.00134 mol), 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (916 mg, 0.00202 mol), xantphos (237 mg, 0.000410 mol), tris(dibenzylideneacetone)dipalladium(0) (147 mg, 0.000160 mol), and potassium phosphate (510 mg, 0.00240 mol) in 1,4-Dioxane (6.0 mL) was flushed with argon. The mixture was microwaved at 300 watts, 130° C. for 15 minutes. The reaction mixture was filtered, concentrated and purified by preparative HPLC to yield 582 mg of 5-bromo-N-(1-cyclohexyl-5-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-amine as the bis-TFA salt.

Workup

  1. customwas flushed with argon
  2. customThe mixture was microwaved at 300 watts, 130° C. for 15 minutes
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-677dbb9bd4d6467696cd18dd044b177e
Source dataset
uspto-grants-2012_10
Patent number
US08293923B2

Reaction notes

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