Diisopropylethylamine → HCID 67817151, compound

HRID 2284548Notes

Reaction equation

HRID 2284548 reaction equation
BrCCC[C:5]1[CH:15]=[CH:14][CH:13]=[C:7]2[C:8]([NH:10][C:11](=[O:12])[C:6]=12)=[O:9].[CH:16](N(CC)C(C)C)([CH3:18])[CH3:17].[CH3:25][O:26][C:27]1[CH:58]=[C:57]([O:59][CH3:60])[CH:56]=[CH:55][C:28]=1[CH2:29][NH:30][C:31]1[C:32]2[CH:39]=[CH:38][N:37]([C@H:40]3[C@H:47]4[C@H:43]([O:44][C:45]([CH3:49])([CH3:48])[O:46]4)[C@@H:42]([CH2:50][NH:51][CH:52]([CH3:54])[CH3:53])[O:41]3)[C:33]=2[N:34]=[CH:35][N:36]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(#N)CC.C(OCC)(=O)C>[CH3:25][O:26][C:27]1[CH:58]=[C:57]([O:59][CH3:60])[CH:56]=[CH:55][C:28]=1[CH2:29][NH:30][C:31]1[C:32]2[CH:39]=[CH:38][N:37]([C@H:40]3[C@@H:47]4[O:46][C:45]([CH3:48])([CH3:49])[O:44][C@@H:43]4[C@@H:42]([CH2:50][N:51]([CH:52]([CH3:54])[CH3:53])[CH2:17][CH2:16][CH2:18][N:10]4[C:11](=[O:12])[C:6]5[C:7](=[CH:13][CH:14]=[CH:15][CH:5]=5)[C:8]4=[O:9])[O:41]3)[C:33]=2[N:34]=[CH:35][N:36]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 21958088BromopropylphthalimideHCID 67814832HCID 67814832, compound

Product 1

HCID 67817151HCID 67817151, compoundYield 72.1%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 7854PropionitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of γ-bromopropylphthalimide (2.37 g, 8.85 mmol), tetra-n-butylammonium iodide (0.234 g, 0.632 mmol), N,N-diisopropylethylamine (1.40 mL, 8.04 mmol) and N-(2,4-dimethoxybenzyl)-7-((3aR,4R,6R,6aR)-6-((isopropylamino)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (3.42 g, 6.32 mmol) was taken up in propanenitrile (25 mL) and was heated at 95° C. After 48 h at 95° C., HPLC indicated that the reaction was nearly complete. The reaction mixture was cooled to room temperature, the mixture was diluted with 200 mL ethyl acetate and washed with two 100 mL portions of H2O and 100 mL brine. The organic phase was dried over Na2SO4, filtered and concentrated to yield a glass. The crude material was purified by flash chromatography (250 g silica gel, 2-4% 7N NH3 in CH3OH/CH2Cl2) to yield the title compound (3.12 g, 72%) as a foam: MS (ESI+) for C37H44N6O7 m/z 685.2 (M+H)+, (ESI−) for C37H44N6O7 m/z 729 (M+HCO2)−; HPLC purity 99% (ret. time, 3.17 min).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with two 100 mL portions of H2O and 100 mL brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield a glass
  7. customThe crude material was purified by flash chromatography (250 g silica gel, 2-4% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-4296fc6052d54cc296ed9c6da66d05fd
Source dataset
uspto-grants-2015_09
Patent number
US09145438B2

Reaction notes

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