1,8-Diazabicyclo(5.4.0)undec-7-ene → {1-(Ethylsulfonyl)-3-[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile

HRID 1966193Notes

Reaction equation

HRID 1966193 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[C:7]3[CH:14]=[CH:13][N:12](COCC[Si](C)(C)C)[C:8]=3[N:9]=[CH:10][N:11]=2)=[CH:2]1.[CH2:23]([S:25]([N:28]1[CH2:31][C:30](=[CH:32][C:33]#[N:34])[CH2:29]1)(=[O:27])=[O:26])[CH3:24].N12CCCN=C1CCCCC2>C(#N)C>[CH2:23]([S:25]([N:28]1[CH2:29][C:30]([CH2:32][C:33]#[N:34])([N:1]2[CH:5]=[CH:4][C:3]([C:6]3[C:7]4[CH:14]=[CH:13][NH:12][C:8]=4[N:9]=[CH:10][N:11]=3)=[CH:2]2)[CH2:31]1)(=[O:26])=[O:27])[CH3:24]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 578688542-(1-(Ethylsulfonyl)azetidin-3-ylidene)acetonitrileHCID 584312944-(1H-pyrrol-3-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 44232361{1-(Ethylsulfonyl)-3-[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 4-(1H-pyrrol-3-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.100 g, 0.318 mmol) and [1-(ethylsulfonyl)azetidin-3-ylidene]acetonitrile (0.118 g, 0.636 mmol, prepared as in Example 68) in acetonitrile (1 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (24 μL, 0.16 mmol). The mixture was stirred for 4 hours. The solvent was evaporated. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution, then extracted with two further portions of ethyl acetate. The combined extracts were dried over sodium sulfate, decanted and concentrated. The crude product was stirred with 25% TFA/DCM (8 mL) overnight. The solvents were evaporated. The product was then stirred with ethylenediamine (0.3 mL) in methanol (5 mL). Preparative HPLC-MS (eluting with a gradient of methanol and water containing 0.15% NH4OH) was used to purify the product. 1H NMR (300 MHz, CDCl3): δ 8.59 (s, 1H), 7.54 (dd, 1H), 7.27 (d, 1H), 6.95 (dd, 1H), 6.82 (dd, 1H), 6.74 (d, 1H), 4.49 (d, 2H), 4.15 (d, 2H), 3.24 (s, 2H), 3.02 (q, 2H), 1.33 (t, 3H); LCMS (M+H)+: 371.1.

Workup

  1. customThe solvent was evaporated
  2. customThe residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution
  3. extractionextracted with two further portions of ethyl acetate
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. stirringThe crude product was stirred with 25% TFA/DCM (8 mL) overnight
  8. customThe solvents were evaporated
  9. stirringThe product was then stirred with ethylenediamine (0.3 mL) in methanol (5 mL)
  10. washPreparative HPLC-MS (eluting with a gradient of methanol and water containing 0.15% NH4OH)
  11. customto purify the product

Sources & evidence

ORD record
ord-97f9dbe49298412b9248a659e56e4682
Source dataset
uspto-grants-2013_04
Patent number
US08420629B2

Reaction notes

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