Sodium Carbonate → (S)-6a-ethyl-5-methyl-2-(2-(3-(pyridin-3-yl)phenyl)-1H-imidazol-1-yl)-6a,7,8,9-tetrahydropyrrolo[2,1-h]pteridin-6(5H)-one

HRID 44886Notes

Reaction equation

HRID 44886 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[N:9]([C:13]3[N:22]=[CH:21][C:20]4[N:19]([CH3:23])[C:18](=[O:24])[C@:17]5([CH2:28][CH3:29])[CH2:25][CH2:26][CH2:27][N:16]5[C:15]=4[N:14]=3)[CH:10]=[CH:11][N:12]=2)[CH:5]=[CH:6][CH:7]=1.[N:30]1[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:28]([C@@:17]12[CH2:25][CH2:26][CH2:27][N:16]1[C:15]1[N:14]=[C:13]([N:9]3[CH:10]=[CH:11][N:12]=[C:8]3[C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:32]4[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=4)[CH:3]=3)[N:22]=[CH:21][C:20]=1[N:19]([CH3:23])[C:18]2=[O:24])[CH3:29]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 58405315(S)-2-(2-(3-bromophenyl)-1H-imidazol-1-yl)-6a-ethyl-5-methyl-6a,7,8,9-tetrahydropyrrolo[2,1-h]pteridin-6(5H)-one

Product 1

HCID 58405346(S)-6a-ethyl-5-methyl-2-(2-(3-(pyridin-3-yl)phenyl)-1H-imidazol-1-yl)-6a,7,8,9-tetrahydropyrrolo[2,1-h]pteridin-6(5H)-oneYield 38%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

(S)-2-(2-(3-bromophenyl)-1H-imidazol-1-yl)-6a-ethyl-5-methyl-6a,7,8,9-tetrahydropyrrolo[2,1-h]pteridin-6(5H)-one (Example 252, 0.118 mmol, 0.053 g) was added to a solution of 3-pyridyl boronic acid (0.593 mmol, 0.072 g), Na2CO3 (0.593 mmol, 0.063 g), and Pd(PPh3)4 (0.029 mmol, 0.034 g) in 1 mL of DME and 0.5 mL of H2O. The reaction mixture was microwaved for 40 minutes at 135° C. The reaction mixture was diluted with 15 mL of DCM, washed with 5 mL of H2O, dried with Na2SO4, filtered and concentrated. The resulting residue was purified by reverse phase HPLC to give the title compound as a white solid (0.020 g, 38%); 1H NMR (400 MHz, CDCl3) δ: 9.18 (s, 1H), 8.77 (m, 1H), 8.70 (m, 1H), 8.22 (s, 1H), 7.93 (s, 1H), 7.87 (m, 1H), 7.82 (m, 1H), 7.73 (s, 1H), 7.56 (m, 3H), 3.38 (m, 3H), 3.29 (m, 1H), 2.24 (m, 2H), 2.00 (m, 2H), 1.77 (m, 1H), 1.62 (m, 1H), 0.78 (t, J=7.4 Hz, 3H); LCMS: 452.3 m/z (M+H)+; ret. Time: 3.758 min (Analytical Method C).

Workup

  1. customThe reaction mixture was microwaved for 40 minutes at 135° C
  2. washwashed with 5 mL of H2O
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-fc620ea9144c4b39b1f113f30fb92958
Source dataset
uspto-grants-2013_09
Patent number
US08541418B2

Reaction notes

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