Triethylamine → 2,4-Dichloro-7-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidine

HRID 1022452Notes

Reaction equation

HRID 1022452 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([Cl:11])[C:5]2[CH:10]=[CH:9][NH:8][C:6]=2[N:7]=1.C(N(CC)CC)C.[CH:19]1(B(O)O)[CH2:21][CH2:20]1>C(Cl)Cl.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[N:3]=[C:4]([Cl:11])[C:5]2[CH:10]=[CH:9][N:8]([CH:19]3[CH2:21][CH2:20]3)[C:6]=2[N:7]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 2760897Cyclopropylboronic acid2×HCID 141168712,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 583988902,4-Dichloro-7-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidineYield 27.5%

Reagents, catalysts & solvents 2

HCID 165397Cupric acetate monohydrateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (210 mg, 1.12 mmol) in methylene chloride (4.86 mL) was treated with triethylamine (314 μL, 2.26 mmol), copper(II) acetate monohydrate (232 mg, 1.16 mmol) and cyclopropylboronic acid (95.9 mg, 1.12 mmol). The reaction was stirred at room temperature overnight. At this time, the reaction was warmed to 70° C. for 3 h. At this time, the reaction was treated with additional triethylamine (314 μL, 2.26 mmol), copper(II) acetate monohydrate (232 mg, 1.16 mmol) and cyclopropylboronic acid (95.9 mg, 1.12 mmol). The reaction was allowed to stir overnight at room temperature. At this time, the reaction was filtered through a plug of Celite®, washing with a 10% methanol/methylene chloride solution. The filtrate was concentrated in vacuo onto silica gel. Flash chromatography (24 g silica gel column, 2-20% ethyl acetate/hexanes) afforded 2,4-dichloro-7-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidine as an off-white solid (70 mg, 27.5%). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.82-1.28 (m, 4H) 3.62 (s, 1H) 6.66 (d, J=3.58 Hz, 1H) 7.73 (d, J=3.39 Hz, 1H). LC-MS calcd. for C9H8Cl2N3 [(M+H)+] 228, obsd. 227.9.

Workup

  1. temperatureAt this time, the reaction was warmed to 70° C. for 3 h
  2. stirringto stir overnight at room temperature
  3. filtrationAt this time, the reaction was filtered through a plug of Celite®
  4. washwashing with a 10% methanol/methylene chloride solution
  5. concentrationThe filtrate was concentrated in vacuo onto silica gel

Sources & evidence

ORD record
ord-95dc668edd834aa0a49bc309e48f544a
Source dataset
uspto-grants-2014_05
Patent number
US08722661B2

Reaction notes

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