Sodium hydride → 2,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

HRID 529639Notes

Reaction equation

HRID 529639 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[C:10]([I:11])=[CH:9][NH:8][C:6]=2[N:7]=1.[CH3:13][Si:14]([CH2:17][CH2:18][O:19][CH2:20]Cl)([CH3:16])[CH3:15].[H-].[Na+].[NH4+].[Cl-]>O.C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[C:10]([I:11])=[CH:9][N:8]([CH2:20][O:19][CH2:18][CH2:17][Si:14]([CH3:16])([CH3:15])[CH3:13])[C:6]=2[N:7]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 574159022,4-Dichloro-5-iodo-7H-pyrrolo(2,3-d)pyrimidine

Product 1

HCID 866796212,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidineYield 54.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

A 50-L jacketed reactor was flushed with nitrogen and charged with 2,4-dichloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (1437 g, 4578 mmol), anhydrous DMF (5.75 L) and SEM-Cl (1145 g, 6867 mmol). The reaction solution was cooled to 0-5° C. and treated with sodium hydride (60% dispersion in mineral oil, 275 g, 6867 mmol) portion wise over 2 h. The mixture was allowed to warm to room temperature over 1 h, after which time TLC analysis indicated complete reaction. The reaction mixture was treated with saturated aqueous NH4Cl (4.5 L), diluted with water (14 L), and stirred at room temperature for 16 h to give a brown precipitate. The precipitate was filtered and washed with water (3×3 L) and hexanes (2×3 L) to give 2065 g of a crude brown solid. The crude solid was dissolved in DCM (3 L), and the solution was filtered to remove insoluble material and concentrated to a solid. The solid was triturated twice from methanol/water (4 L, 5:1) and dried under reduced pressure at 45° C. for 64 h to afford 1100 g (Yield: 54%) of the title compound as a beige solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.14 (s, 1H), 5.54 (s, 2H), 3.52 (t, J=7.94 Hz, 2H), 0.84 (t, J=7.94 Hz, 2H), −0.08 (s, 9H). MS (ESI) m/z 443.9 [M+1]+.

Workup

  1. customA 50-L jacketed reactor was flushed with nitrogen
  2. temperatureto warm to room temperature over 1 h
  3. customreaction
  4. customto give a brown precipitate
  5. filtrationThe precipitate was filtered
  6. washwashed with water (3×3 L) and hexanes (2×3 L)
  7. customto give 2065 g of a crude brown solid
  8. filtrationthe solution was filtered
  9. customto remove insoluble material
  10. concentrationconcentrated to a solid
  11. customThe solid was triturated twice from methanol/water (4 L, 5:1)
  12. customdried under reduced pressure at 45° C. for 64 h

Sources & evidence

ORD record
ord-07eb2f0451c24c54b2740c57bcfed2ea
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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