Acetophenone → (R)-8-cyclopentyl-7-ethyl-5-methyl-2-(2-oxo-2-phenylethyl)-7,8-dihydropteridin-6(5H)-one

HRID 44802Notes

Reaction equation

Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH3:12])[C:7](=[O:13])[C@@H:6]([CH2:14][CH3:15])[N:5]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:4]=2[N:3]=1.[C:21]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=[O:23])[CH3:22].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.O.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:16]1([N:5]2[C:4]3[N:3]=[C:2]([CH2:22][C:21](=[O:23])[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[N:11]=[CH:10][C:9]=3[N:8]([CH3:12])[C:7](=[O:13])[C@H:6]2[CH2:14][CH3:15])[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

Conditions

Temperature: 120 °C

Procedure

5.0 g of Intermediate B, 2.5 eq of acetophenone, 0.05 eq of Pd2(dba)3, 0.1 eq of BINAP and 2.0 eq of Cs2CO3 were suspended in a mixture of 50 mL toluene and 10 mL of water, then heated to 120° C. under N2 for 60 hours. After cooling to rt, added 100 mL of water and washed the organic phase, dried with anhydrous Na2SO4, concentrated and purified by silica gel column (PE:EA=3:1) to give the pure Intermediate B-1 (1.2 g, 19%) as yellow solid.

Workup

temperatureAfter cooling to rt
washwashed the organic phase
dry with materialdried with anhydrous Na2SO4
concentrationconcentrated
custompurified by silica gel column (PE:EA=3:1)
customto give the pure Intermediate B-1 (1.2 g, 19%) as yellow solid

Sources & evidence

ORD record: ord-9b67419a75cc498ca8a214e9a6d980ca
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541418B2

Reaction notes

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