Acetyl chloride → US9777003, Example 106

HRID 628370Notes

Reaction equation

HRID 628370 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[Cl:5][C:6]1[CH:7]=[C:8]([CH:35]=[CH:36][CH:37]=1)[CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:19]([CH3:22])=[N:20][N:21]=3)[C:13]=2[CH:12]=[C:11]1[C:23]1[CH:27]=[CH:26][N:25]([C:28]2([CH2:32][C:33]#[N:34])[CH2:31][NH:30][CH2:29]2)[N:24]=1.C(N(CC)CC)C>C(Cl)Cl>[C:1]([N:30]1[CH2:31][C:28]([CH2:32][C:33]#[N:34])([N:25]2[CH:26]=[CH:27][C:23]([C:11]3[N:10]([CH2:9][C:8]4[CH:35]=[CH:36][CH:37]=[C:6]([Cl:5])[CH:7]=4)[C:14]4[CH:15]=[CH:16][C:17]5[N:18]([C:19]([CH3:22])=[N:20][N:21]=5)[C:13]=4[CH:12]=3)=[N:24]2)[CH2:29]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 118159592US10442803, Example 157

Product 1

HCID 118159488US9777003, Example 106Yield 61.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acetyl chloride (1.1 μL, 0.016 mmol, Aldrich) in DCM (0.35 mL) was added to (3-{3-[6-(3-chlorobenzyl)-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridin-7-yl]-1H-pyrazol-1-yl}azetidin-3-yl)acetonitrile (6.0 mg, 0.013 mmol, from Step 1). Triethylamine (3.7 μL, 0.026 mmol) was then added and the reaction was stirred for 10 minutes. Purification via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) afforded product (4.0 mg, 61%).

Workup

  1. customPurification via preparative HPLC-MS (C18
  2. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-164a12c1c7b04115bc4b70e917c81c86
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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