Dimethylformamide → HCID 58180927, compound

HRID 1772833Notes

Reaction equation

HRID 1772833 reaction equation
[C:1]([CH:3]=[CH:4][CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH:7]1[CH2:19][O:20][CH3:21])#[N:2].[NH:22]1[CH:26]=[C:25]([C:27]2[C:28]3[CH:35]=[CH:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:29]=3[N:30]=[CH:31][N:32]=2)[CH:24]=[N:23]1.CN(C=O)C.C(=O)([O-])[O-].[K+].[K+]>>[C:1]([CH2:3][CH:4]([N:22]1[CH:26]=[C:25]([C:27]2[C:28]3[CH:35]=[CH:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:29]=3[N:30]=[CH:31][N:32]=2)[CH:24]=[N:23]1)[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])[CH2:8][CH:7]1[CH2:19][O:20][CH3:21])#[N:2]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 67054935HCID 67054935, compound

Product 1

HCID 58180927HCID 58180927, compound

Procedure

A mixture of tert-butyl 4-[3-cyanoprop-2-en-1-yl]-3-(methoxymethyl)piperazine-1-carboxylate (54 mg, 0.18 mmol; as a mixture of E- and Z-olefin isomers from Step 2) and 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (58 mg, 0.18 mmol, prepared as described in WO 2007/070514 Example 65) in DMF (0.28 mL, 3.6 mmol) was treated with potassium carbonate (0.081 g, 0.58 mmol) and stirred for 5 h. The mixture was filtered and the filtrate was diluted with EtOAc, which was then washed with water (3 times), brine (once), dried over sodium sulfate, decanted and concentrated. Flash chromatography, using a 12 g silica gel cartridge and eluting with a gradient of 0-100% EtOAc in hexanes afforded an impure mixture of diastereomers which was used without further purification in the next step (91 mg, 57%). LCMS (M+H)+: 611.3.

Workup

  1. filtrationThe mixture was filtered
  2. additionthe filtrate was diluted with EtOAc, which
  3. washwas then washed with water (3 times), brine (once),
  4. dry with materialdried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. washeluting with a gradient of 0-100% EtOAc in hexanes
  8. customafforded
  9. additionan impure mixture of diastereomers which
  10. customwas used without further purification in the next step (91 mg, 57%)

Sources & evidence

ORD record
ord-57094482f49549b7addb8e87435f71a4
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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