Tetrahydrofuran → 4-[1-(1-ethylbut-3-en-1-yl)-1H-pyrazol-4-yl]-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine

HRID 1501469Notes

Reaction equation

HRID 1501469 reaction equation
[CH2:1]1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:16][Si:17]([CH3:43])([CH3:42])[CH2:18][CH2:19][O:20][CH2:21][N:22]1[C:26]2[N:27]=[CH:28][N:29]=[C:30]([C:31]3[CH:32]=[N:33][N:34]([CH:36]([CH2:40][CH3:41])[CH2:37][CH:38]=O)[CH:35]=3)[C:25]=2[CH:24]=[CH:23]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1>[CH2:40]([CH:36]([N:34]1[CH:35]=[C:31]([C:30]2[C:25]3[CH:24]=[CH:23][N:22]([CH2:21][O:20][CH2:19][CH2:18][Si:17]([CH3:16])([CH3:42])[CH3:43])[C:26]=3[N:27]=[CH:28][N:29]=2)[CH:32]=[N:33]1)[CH2:37][CH:38]=[CH2:1])[CH3:41]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 3251421Potassium bis(trimethylsilyl)amideHCID 574778983-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanal

Product 1

HCID 574779104-[1-(1-ethylbut-3-en-1-yl)-1H-pyrazol-4-yl]-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidineYield 188.6%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To an ice cooled solution of methyl triphenylphosphonium bromide (100 mg, 0.0004 mol) in THF (2 mL, 0.02 mol) was added 0.5 M potassium bis(trimethylsilyl)amide in toluene (0.8 mL). The mixture was stirred for 1 h at 0° C. ice bath, and was then cooled to −78° C. and treated with 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanal (80 mg, 0.0002 mol) (from Example 498). The reaction was stirred at −78° C. and gradually was warmed to room temperature overnight. The reaction was partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated to give 4-[1-(1-ethylbut-3-en-1-yl)-1H-pyrazol-4-yl]-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine 150 mg as a crude product. LC/MS=398 (M+1).

Workup

  1. temperaturewas then cooled to −78° C.
  2. stirringThe reaction was stirred at −78° C.
  3. temperaturegradually was warmed to room temperature overnight
  4. customThe reaction was partitioned between water and ethyl acetate
  5. washThe organic layer was washed with saturated sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ba92a5682ccf430e8c74525c5688701a
Source dataset
uspto-grants-2015_12
Patent number
US09206187B2

Reaction notes

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