Sodium hydride → HCID 178463586, compound

HRID 634454Notes

Reaction equation

HRID 634454 reaction equation
C([N:20]1[CH:28]=[N:27][C:26]2[C:21]1=[N:22][CH:23]=[N:24][C:25]=2[NH:29]C(=O)OC(C)(C)C)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].Br.Br[CH:41]([C:43]1[O:44][C:45](=[O:65])[C:46]2[C:51]([C:52]=1[C:53]1[S:54][C:55]([CH2:58][N:59]3[CH2:64][CH2:63][O:62][CH2:61][CH2:60]3)=[CH:56][CH:57]=1)=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH3:42]>CN(C)C=O.[Cl-].[Na+].O>[N:24]1[C:25]([NH:29][CH:41]([C:43]2[O:44][C:45](=[O:65])[C:46]3[C:51]([C:52]=2[C:53]2[S:54][C:55]([CH2:58][N:59]4[CH2:60][CH2:61][O:62][CH2:63][CH2:64]4)=[CH:56][CH:57]=2)=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH3:42])=[C:26]2[C:21]([NH:20][CH:28]=[N:27]2)=[N:22][CH:23]=1

Participants

6

Reactant 3

HCID 24758Sodium hydride2×HCID 70974658tert-butyl N-(9-tritylpurin-6-yl)carbamateHCID 1181312913-(1-Bromoethyl)-4-(5-(morpholinomethyl)thiophen-2-yl)-1H-isochromen-1-one hydrobromide

Product 1

HCID 178463586HCID 178463586, compoundYield 9.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

tert-Butyl 9-trityl-9H-purin-6-ylcarbamate (102 mg, 0.213 mmol) was added to a solution of 50% dispersion in mineral oil NaH (5.12 mg, 0.213 mmol) in N,N-dimethylformamide (0.5 ml) and the mixture was stirred at RT for 30 min. 3-(1-Bromoethyl)-4-(5-(morpholinomethyl)thiophen-2-yl)-1H-isochromen-1-one hydrobromide (intermediate C16, 100 mg, 0.194 mmol) was suspended in DMF (0.5 ml, 0.194 mmol) and reacted with 50% dispersion in mineral oil NaH (5.1 mg, 0.213 mmol) at RT for 15 min. The resulting solution was added to the previous prepared mixture and left on stirring at 60° C. for 1 hrs, at RT for 3 hrs and then at 80° C. for 3 hrs. The reaction mixture was poured into brine and extracted with EtOAc. The collected organic phases were dried and concentrated. The resulting crude material was purified under reverse phase chromatography using a Biotage C18 60 g SNAP cartridge. The collected fractions were added with 37% HClaqueous (1 ml) and concentrated. The resulting material was further purified under reverse phase chromatography using a Biotage C18 30 g SNAP cartridge. The resulting material was finally purified on silica with a gradient of DCM and 2-propanol, modified with 0.5% TEA, to give the title compound (9 mg, 9.5%).

Workup

  1. additionThe resulting solution was added to the previous prepared mixture
  2. waitleft
  3. stirringon stirring at 60° C. for 1 hrs, at RT for 3 hrs
  4. waitat 80° C. for 3 hrs
  5. extractionextracted with EtOAc
  6. customThe collected organic phases were dried
  7. concentrationconcentrated
  8. customThe resulting crude material was purified under reverse phase chromatography
  9. additionThe collected fractions were added with 37% HClaqueous (1 ml)
  10. concentrationconcentrated
  11. customThe resulting material was further purified under reverse phase chromatography
  12. customThe resulting material was finally purified on silica with a gradient of DCM and 2-propanol

Sources & evidence

ORD record
ord-80153b58d8164466b5108c909feb815b
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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