Potassium Phosphate, Tribasic → tert-Butyl {(3R)-1-[5-(2-chlorobenzyl)-7-(4-methoxyphenyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate

HRID 1819318Notes

Reaction equation

HRID 1819318 reaction equation
F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.Br[C:39]1[C:43]2[N:44]([CH3:51])[C:45](=[O:50])[N:46]([CH3:49])[C:47](=[O:48])[C:42]=2[N:41]([CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2[Cl:59])[C:40]=1[N:60]1[CH2:65][CH2:64][CH2:63][C@@H:62]([NH:66][C:67](=[O:73])[O:68][C:69]([CH3:72])([CH3:71])[CH3:70])[CH2:61]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[Cl:59][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=1[CH2:52][N:41]1[C:42]2[C:47](=[O:48])[N:46]([CH3:49])[C:45](=[O:50])[N:44]([CH3:51])[C:43]=2[C:39]([C:32]2[CH:33]=[CH:34][C:29]([O:28][CH3:27])=[CH:30][CH:31]=2)=[C:40]1[N:60]1[CH2:65][CH2:64][CH2:63][C@@H:62]([NH:66][C:67](=[O:73])[O:68][C:69]([CH3:71])([CH3:72])[CH3:70])[CH2:61]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 57886890tert-Butyl {(3R)-1-[7-bromo-5-(2-chlorobenzyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate

Product 1

HCID 57886887tert-Butyl {(3R)-1-[5-(2-chlorobenzyl)-7-(4-methoxyphenyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamateYield 10.6%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Bis(dibenzylideneacetone)palladium (18 mg), tri-tert-butylphosphonium tetrafluoroborate (22 mg), potassium phosphate (329 mg) and 4-methoxyphenylboronic acid (236 mg) were added to a solution of tert-butyl {(3R)-1-[7-bromo-5-(2-chlorobenzyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate (90 mg) in dioxane (4 ml), and the resulting mixture was stirred with heating at 50° C. for 15 hours. The reaction solution was filtered through Celite and washed with tetrahydrofuran and the filtrate was concentrated under reduced pressure. A 10% aqueous potassium carbonate solution was added to the residue, followed by two runs of extraction with chloroform (50 ml). The organic layer was dried over sodium sulfate and filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=2/1) to obtain the title compound (10 mg).

Workup

  1. filtrationThe reaction solution was filtered through Celite
  2. washwashed with tetrahydrofuran
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionA 10% aqueous potassium carbonate solution was added to the residue
  5. extractionfollowed by two runs of extraction with chloroform (50 ml)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-aa322a8971a840d59a56e86ac74d9789
Source dataset
uspto-grants-2009_10
Patent number
US07601728B2

Reaction notes

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