1,4-Diiodobutane → 4'-Chlorospiro[cyclopentane-1,5'-pyrrolo[2,3-d]pyrimidin]-6'(7'H)-one

HRID 1685178

Reaction equation

[Cl:1][C:2]1[C:3]2[CH2:10][C:9](=[O:11])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].I[CH2:23][CH2:24][CH2:25][CH2:26]I>C1COCC1>[Cl:1][C:2]1[C:3]2[C:10]3([CH2:26][CH2:25][CH2:24][CH2:23]3)[C:9](=[O:11])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

Add 4-chloro-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one (0.6 g; 0.0035 mol; 1.0 equiv) in anhydrous THF (20 mL) and cool the reaction to −78° C., under an inert atmosphere. Add drop-wise lithium hexamethyldisilazide (8.8 mL; 0.0088 mol; 2.5 equiv; 1M in THF). Stir at −78° C. for 30 min. Add drop-wise 1,4-diiodobutane (0.56 mL; 0.0042 mol; 1.2 equiv), allow the reaction temperature to reach 0° C. slowly, and stir for 2 h. Then allow the reaction to reach RT and stir for additional 1 h. Quench the reaction with saturated ammonium chloride solution and extract with EA. Wash the organic layer with water, brine, and dry over anhydrous sodium sulfate. Evaporate the organic layer and purify over a 10 g silica column with acetone (5%) in DCM. Pool fractions to give the title compound (0.34 g; 43.09%). H NMR (DMSO-d6): 11.68 (1H, s), 8.53 (1H, s), 2.0-2.1 (m, 2H), 1.91-1.99 (m, 6H).

Workup

temperaturecool
customthe reaction to −78° C.
customto reach 0° C.
stirringstir for 2 h
customthe reaction
customto reach RT
stirringstir for additional 1 h
customQuench
customthe reaction with saturated ammonium chloride solution
extractionextract with EA
washWash the organic layer with water, brine
dry with materialdry over anhydrous sodium sulfate
customEvaporate the organic layer
custompurify over a 10 g silica column with acetone (5%) in DCM

Sources & evidence

ORD record: ord-598b35b6448f4efb9b4575838bdc202a
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148387B2

Linked notes

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