Pyridine → 5-[2-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-5-(1-isopropyl-piperidin-4-yloxy)-indol-1-yl]-pyridine-2-carbonitrile

HRID 493990Notes

Reaction equation

HRID 493990 reaction equation
[O:1]=[S:2]1(=[O:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.N1C=CC=CC=1.[C:36]([C:38]1[CH:43]=[CH:42][C:41](B2OC(C)(C)C(C)(C)O2)=[CH:40][N:39]=1)#[N:37]>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[O:29]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([C:41]3[CH:42]=[CH:43][C:38]([C:36]#[N:37])=[N:39][CH:40]=3)[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:27])[CH3:28])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 1049PyridineHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 16739577(1,1-Dioxo-thiomorpholin-4-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

Product 1

HCID 167396085-[2-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-5-(1-isopropyl-piperidin-4-yloxy)-indol-1-yl]-pyridine-2-carbonitrileYield 30.6%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (1,1-dioxo-thiomorpholin-4-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (Example 2, 150 mg, 1.0 eq.), anhydrous copper(II) acetate (131 mg, 2 eq.), pyridine (120 microL, 4 eq.) in dichloromethane (3.5 mL), 2-cyanopyridine-5-boronic acid pinacol ester (247 mg, 3 eq.) was added. The reaction mixture was stirred for 4 days and then concentrated in vacuo. The residue was then purified on silica eluting with dichloromethane/methanol 98:2 v:v. One fraction was isolated and dried in vacuo, to yield 57 mg (23%) of the desired product as light yellow oil. MS (m/e): 522.5 (MH+, 100%).

Workup

  1. additionwas added
  2. concentrationconcentrated in vacuo
  3. customThe residue was then purified on silica eluting with dichloromethane/methanol 98:2 v
  4. customOne fraction was isolated
  5. customdried in vacuo

Sources & evidence

ORD record
ord-7bbeb58ec3ce4bbaa3f7fdac473dd3ca
Source dataset
uspto-grants-2009_05
Patent number
US07538101B2

Reaction notes

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