1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 58431359, compound

HRID 1617352Notes

Reaction equation

HRID 1617352 reaction equation
[C:1]([CH:3]=[C:4]1[CH2:7][N:6]([C:8]2([CH3:21])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH2:5]1)#[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.N12CCCN=C1CCCCC2>C(#N)C>[C:1]([CH2:3][C:4]1([N:22]2[CH:26]=[C:25]([C:27]3[C:28]4[CH:35]=[CH:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:29]=4[N:30]=[CH:31][N:32]=3)[CH:24]=[N:23]2)[CH2:5][N:6]([C:8]2([CH3:21])[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]2)[CH2:7]1)#[N:2]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 58431339HCID 58431339, compound

Product 1

HCID 58431359HCID 58431359, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 2 L round bottom flask fitted with overhead stirring, septa and nitrogen inlet was charged with tert-butyl 4-[3-(cyanomethylene)azetidin-1-yl]-4-methylpiperidine-1-carboxylate (9.17 g, 0.0472 mol), 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (14.9 g, 0.0472 mol) and acetonitrile (300 mL). The resulting solution was heterogeneous. To the solution was added 1,8-diazabicyclo[5.4.0]undec-7-ene (8.48 mL, 0.0567 mol) portionwise via a syringe over 3 minutes at room temperature. The solution slowly became homogeneous and yellow in color. The reaction was allowed to stir at room temperature for 3 hours. The solution was concentrated on a rotovap to remove ˜150 mL of acetonitrile. After addition of 100 mL of EtOAc and 100 mL of 20% brine, the organic phase was separated. The aqueous layer was extracted with 150 mL of EtOAc. The combined organic phase was dried over MgSO4, filtered and concentrated to yield an orange oil. Purification by flash chromatography (150 grams of silica, 60% EtOAc/hexanes, loaded with CH2Cl2) yielded the title compound as a white foam. LC-MS: 607.2 (M+H)+.

Workup

  1. customA 2 L round bottom flask fitted with overhead
  2. stirringto stir at room temperature for 3 hours
  3. concentrationThe solution was concentrated on a rotovap
  4. customto remove ˜150 mL of acetonitrile
  5. additionAfter addition of 100 mL of EtOAc and 100 mL of 20% brine
  6. customthe organic phase was separated
  7. extractionThe aqueous layer was extracted with 150 mL of EtOAc
  8. dry with materialThe combined organic phase was dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto yield an orange oil
  12. customPurification by flash chromatography (150 grams of silica, 60% EtOAc/hexanes, loaded with CH2Cl2)

Sources & evidence

ORD record
ord-255a0800ee7e417c9d4b1766d535bf4c
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

Loading…