Triethylamine → HCID 178447258, compound

HRID 22021

Reaction equation

HRID 22021 reaction equation
[CH3:1][C:2]([CH3:17])([CH3:16])[C:3]([NH:5][C:6]1[NH:11][C:10]2=[N:12][CH:13]=[CH:14][C:9]2=[C:8]([OH:15])[N:7]=1)=[O:4].IN1C(=O)CCC1=O.[CH3:26][Si:27]([C:30]#[CH:31])([CH3:29])[CH3:28].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.OC1C2C(I)=CNC=2N=C(NC(=O)C(C)(C)C)N=1.[Pd](Cl)Cl.O.C(#N)C>[OH:15][C:8]1[C:9]2[C:14]([C:31]#[C:30][Si:27]([CH3:29])([CH3:28])[CH3:26])=[CH:13][NH:12][C:10]=2[N:11]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:17])([CH3:16])[CH3:1])[N:7]=1

Participants

11

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 120273N-IodosuccinimideHCID 178447259HCID 178447259, compound

Product 1

HCID 178447258HCID 178447258, compoundYield 66%

Reagents, catalysts & solvents 5

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolventHCID 178447260HCID 178447260, compoundSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 20.0 g (85.4 mmol) of 2-(2,2-dimethylpropionyl)amino-4-hydroxypyrrolo[2,3-d]pyrimidine in 160 mL of dry DMF stirred in a dry atmosphere was added 38.2 g (187.8 mmol) of BSA and the mixture was heated to 40° C. for 3 hours. After cooling to about 0° C. in an ice bath there was added 23.1 g (102.5 mmol) of N-iodosuccinimide as a solid. The mixture was stirred at 0° C. for 15 minutes, then allowed to warm to ambient temperature overnight. To the resulting mixture, maintained under a nitrogen atmosphere, was added sequentially 12.6 g (128 mmol) of (trimethylsilyl) acetylene, 17.3 g (171 mmol) of triethylamine, 3.25 g (17.1 mmol) of cuprous iodide, and a preformed mixture prepared by adding 1.51 g (8.5 mmol) of palladium (II) chloride and 4.48 g (17.1 mmol) of triphenylphosphine to 40 mL of DMF. The resulting solution was stirred at ambient temperature for 2 hours. At this point, HPLC analysis of an aliquot indicated complete conversion of the in situ-derived N-(4-hydroxy-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropionamide. The reaction mixture was poured into 500 mL of acetonitrile and 12 mL of water was added, causing the product to precipitate. After stirring for about 15 minutes, the product was filtered, washed with acetonitrile, and dried, affording 18.6 g (66%) of N-[4-hydroxy-5-(trimethylsilyl) ethynyl-7H-pyrrolo [2,3-d]pyrimidin-2-yl]-2,2-dimethyl propionamide as a light tan solid, mp>300° C. NMR δ0.18 (s, 9H), 1.22 (s, 9H), 7.33 (s, 1H), 10.9 (br s, 1H), 11.8 (br s, 1H), 11.9 (br s, 1H); IR (KBr) 3229, 2155, 1678, 1658, 1619, 1434, 1244, 1180, 1069 cm-1 ; UV (EtOH) 285 nm (ε15,400 ), 250 nm (ε16,000). Anal. Calcd for C16H22N4O2Si: C, 58.15; H, 6.71; N, 16.95. Found: C, 57.58; H, 6.87; N,16.96.

Workup

  1. additionwas added 38.2 g (187.8 mmol) of BSA
  2. temperatureAfter cooling to about 0° C. in an ice bath
  3. temperatureto warm to ambient temperature overnight
  4. temperatureTo the resulting mixture, maintained under a nitrogen atmosphere
  5. customa preformed mixture prepared
  6. stirringThe resulting solution was stirred at ambient temperature for 2 hours
  7. additionwas added
  8. customto precipitate
  9. stirringAfter stirring for about 15 minutes
  10. filtrationthe product was filtered
  11. washwashed with acetonitrile
  12. customdried

Sources & evidence

ORD record
ord-1873c29c450f48249c7e477f1aadf298
Source dataset
uspto-grants-1995_06
Patent number
US05426187

Linked notes

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