Potassium Carbonate → 3-(1-(6-amino-9H-purin-9-yl)ethyl)-4-(5-(morpholinomethyl)thiophen-2-yl)-1H-isochromen-1-one

HRID 634486Notes

Reaction equation

HRID 634486 reaction equation
Br.Br[CH:3]([C:5]1[O:6][C:7](=[O:27])[C:8]2[C:13]([C:14]=1[C:15]1[S:16][C:17]([CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:18][CH:19]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH3:4].C(OC([N:35](C(OC(C)(C)C)=O)[C:36]1[N:44]=[CH:43][N:42]=[C:41]2[C:37]=1[NH:38][CH:39]=[N:40]2)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:35][C:36]1[N:44]=[CH:43][N:42]=[C:41]2[C:37]=1[N:38]=[CH:39][N:40]2[CH:3]([C:5]1[O:6][C:7](=[O:27])[C:8]2[C:13]([C:14]=1[C:15]1[S:16][C:17]([CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:18][CH:19]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH3:4]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 10497007Di-tert-butyl 7H-purin-6-yl-2-imidodicarbonateHCID 1181312913-(1-Bromoethyl)-4-(5-(morpholinomethyl)thiophen-2-yl)-1H-isochromen-1-one hydrobromide

Product 1

HCID 1181315183-(1-(6-amino-9H-purin-9-yl)ethyl)-4-(5-(morpholinomethyl)thiophen-2-yl)-1H-isochromen-1-oneYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(1-Bromoethyl)-4-(5-(morpholinomethyl)thiophen-2-yl)-1H-isochromen-1-one hydrobromide (intermediate C16, 52 mg, 0.113 mmol), N6,N6-bis(tert-Butoxycarbonyl)-adenine (74.1 mg, 0.221 mmol), K2CO3 (30.5 mg, 0.221 mmol) were reacted in DMF (0.5 ml) at 80° C. The crude was purified via reverse phase chromatography with a Biotage C18 30 g SNAP column (Phase A, water 95%, ACN 5%, formic acid 0.1%); Phase B ACN 95%, water 5%, formic acid 0.1%) and recovered material was then treated with HCl 37% before evaporation to give a crude that was further purified via reverse phase chromatography with a Biotage C18 12 g SNAP column (Phase A, water 95%, ACN 5%, formic acid 0.1%); Phase B ACN 95%, water 5%, formic acid 0.1%) to give the title compound (25 mg, 69%).

Workup

  1. customThe crude was purified via reverse phase chromatography with a Biotage C18 30 g SNAP column (Phase A, water 95%, ACN 5%, formic acid 0.1%)
  2. customPhase B ACN 95%, water 5%, formic acid 0.1%) and recovered material
  3. additionwas then treated with HCl 37% before evaporation
  4. customto give a crude that
  5. customwas further purified via reverse phase chromatography with a Biotage C18 12 g SNAP column (Phase A, water 95%, ACN 5%, formic acid 0.1%)

Sources & evidence

ORD record
ord-6aed001b93124076b6acb7a802d27cca
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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