Tert-Butyl nitrite → HCID 178506018, compound
Reaction equation
N[C:2]1[NH:7][C:6]2=[CH:8][CH:9]=[N:10][C:5]2=[C:4]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:3]=1.N1C=CC=CC=1.[FH:25].N(OC(C)(C)C)=O.[Br:33]N1C(=O)CCC1=O>N1C=CC=CC=1.O1CCCC1>[CH2:12]([O:11][C:4]1[N:3]=[C:2]([F:25])[NH:7][C:6]2=[C:8]([Br:33])[CH:9]=[N:10][C:5]=12)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1Participants
Procedure
A solution of 2-amino-4-benzyloxypyrrolo[3,2-d]pyrimidine (0.85 g) (Example 12) in dry pyridine (20 mL) was treated with hydrogen fluoride-pyridine and tert-butyl nitrite as described in Example 13. A solution of the crude product in tetrahydrofuran (30 mL) was cooled in an ice bath while N-bromosuccinimide (0.6 g) was added portion-wise. The solution was concentrated and chromatography afforded 4-benzyloxy-7-bromo-2-fluoropyrrolo[3,2-d]pyrimidine (0.8 g) as a solid. A solution of this material (0.74 g) in tetrahydrofuran (30 mL) was cooled in an ice bath while sodium hydride (0.11 g, 60% dispersion) and then tert-butyldimethylsilyl chloride (0.41 g) were added. After 1 h methylene chloride (50 mL) was added and the reaction was quenched with water, then washed with additional water. Normal processing and chromatography afforded 4-benzyloxy-7-bromo-5-N-tert-butyldimethylsilyl-2-fluoropyrrolo[3,2-d]pyrimidine (0.82 g) as a solid. 13C NMR (CDCl3) δ 158.4 (JC,F=17 Hz), 157.5 (JC,F=212 Hz), 153.5 (JC,F=16 Hz), 137.7, 134.9, 130.5, 129.4, 129.0, 118.0, 93.3, 70.3, 26.6, 19.2, −1.9, −2.3.
Workup
- additionwas added portion-wise
- concentrationThe solution was concentrated
Sources & evidence
- ORD record
- ord-549f3038b9704fcd934b7f584089bd4f
- Source dataset
- uspto-grants-2007_05
- Patent number
- US07211677B2
Reaction notes
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