1,3-Dibromopropane → HCID 11562562, compound

HRID 1478232Notes

Reaction equation

HRID 1478232 reaction equation
[F:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7]([CH2:11][C:12]3[C:20]([I:21])=[CH:19][C:15]4[O:16][CH2:17][O:18][C:14]=4[CH:13]=3)=[N:8]2)=[C:4]([NH2:22])[N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:30][CH2:31][CH2:32]Br>CN(C=O)C>[F:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:11][C:12]3[C:20]([I:21])=[CH:19][C:15]4[O:16][CH2:17][O:18][C:14]=4[CH:13]=3)[N:8]2[CH2:30][CH2:31][CH2:32][NH:6][CH:5]([CH3:9])[CH3:4])=[C:4]([NH2:22])[N:3]=1

Participants

5

Reactant 3

HCID 80011,3-DibromopropaneHCID 10796Cesium carbonateHCID 11596767HCID 11596767, compound

Product 1

HCID 11562562HCID 11562562, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-Fluoro-8-(6-iodo-benzo[1,3]dioxol-5-ylmethyl)adenine (300 mg, 0.726 mmol), Cs2CO3 (285 mg, 0.87 mmol) and 1,3-dibromopropane (370 L, 3.63 mmol) in anhydrous DMF (5 mL) was stirred at 50° C. for 2 h. Following solvent removal, product (330 mg, 85%) was collected through silica gel column purification (CHC13 then EtOAc:hexanes:CHC13:i-PrOH at 4:2:4:0.4). MS m/z 534.0 (M+H)+. To this product, i-PrNH2 (10 mL) was added in excess and the resulting solution stirred at room temperature for 1 h. Excess amine was removed and product (230 mg, 75%) collected through silica gel column purification (CHC13:EtOAc:i-PrOH:NH4OH at 4:4:2:0.3). 1H NMR (400 MHz, CDC13) 7.29 (s, 1H), 6.59 (s, 1H), 5.94 (s, 2H), 5.89 (bs, 2H), 4.25 (s, 2H), 4.11 (t, J=7.0 Hz, 2H), 2.73-2.60 (m, 1H), 2.55 (t, J=6.8 Hz, 1H), 1.93-1.86 (m, 2H), 1.03-1.02 (d, J=6.0 Hz, 6H); 13C NMR (100 MHz, methanol-d4) 160.0, 158.4, 157.2, 152.4, 151.3, 149.4, 148.4, 133.1, 118.7, 110.6, 102.4, 88.5, 42.8, 40.1, 38.8, 27.6, 19.4; MS m/z 513.2 (M+H)+. HPLC: (a) 98.5% (60% water-40% acetonitrile); (b) 97.2% (20% to 50% acetonitrile).

Workup

  1. customFollowing solvent removal, product (330 mg, 85%)
  2. customwas collected through silica gel column purification (CHC13 then EtOAc
  3. additionTo this product, i-PrNH2 (10 mL) was added in excess and the resulting solution
  4. customExcess amine was removed
  5. customproduct (230 mg, 75%) collected through silica gel column purification (CHC13:EtOAc:i-PrOH:NH4OH at 4:4:2:0.3)

Sources & evidence

ORD record
ord-dd0e62f5fc344f25bf5ec927d9c031a7
Source dataset
uspto-grants-2016_08
Patent number
US09403828B2

Reaction notes

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