Diisopropylethylamine → HCID 58558077, compound

HRID 1969634Notes

Reaction equation

HRID 1969634 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].[CH3:12][C@H:13]1[C@@H:17]([C:18]2[N:22]3[C:23]4[CH:29]=[CH:28][N:27]([S:30]([C:33]5[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=5)(=[O:32])=[O:31])[C:24]=4[N:25]=[CH:26][C:21]3=[N:20][N:19]=2)[CH2:16][C@@H:15]([NH2:40])[CH2:14]1.CCN(C(C)C)C(C)C>C(Cl)Cl.CC#N.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:12][C@H:13]1[C@@H:17]([C:18]2[N:22]3[C:23]4[CH:29]=[CH:28][N:27]([S:30]([C:33]5[CH:34]=[CH:35][C:36]([CH3:37])=[CH:38][CH:39]=5)(=[O:32])=[O:31])[C:24]=4[N:25]=[CH:26][C:21]3=[N:20][N:19]=2)[CH2:16][C@@H:15]([NH:40][C:5]2[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=2)[C:1]#[N:2])[CH2:14]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27343253-Cyanophenylboronic acidHCID 58557192HCID 58557192, compound

Product 1

HCID 58558077HCID 58558077, compoundYield 65.2%

Reagents, catalysts & solvents 3

HCID 165397Cupric acetate monohydrateCatalyst2×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 3-cyanophenylboronic acid (0.143 g, 0.974 mmol) in DCM (4 mL) was added copper (II) acetate monohydrate (0.013 g, 0.122 mmol) and 4 Å molecular sieves. The reaction mixture was purged 3 times with oxygen. A solution of (1S,3R,4S)-3-methyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]-triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (0.20 g, 0.48 mmol, Preparation #19.2) and DIEA (0.085 mL, 0.487 mmol) in MeCN (1 mL) was added and the reaction mixture was heated at about 45° C. for about 18 h. Additional copper (II) acetate monohydrate (0.013 g, 0.122 mmol) was added and the reaction mixture was stirred for about 4 h. The reaction mixture was filtered through a pad of Celite® and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-60% EtOAc in DCM to give 3-((1S,3R,4S)-3-methyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)benzonitrile (0.16 g, 48%) as a dark brown solid: LC/MS (Table 1, Method c) Rt=1.54 min; MS m/z: 512 (M+H)+.

Workup

  1. customThe reaction mixture was purged 3 times with oxygen
  2. filtrationThe reaction mixture was filtered through a pad of Celite® and concd under reduced pressure
  3. customThe crude material was purified by silica gel chromatography
  4. washeluting with a gradient of 0-60% EtOAc in DCM

Sources & evidence

ORD record
ord-6fc9f15262354d03a46e25545e7c78c8
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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