Pyridine → HCID 86727125, compound

HRID 1054491Notes

Reaction equation

HRID 1054491 reaction equation
Cl.[CH3:2][N:3]1[C:11](=[O:12])[C:10]2[N:9]([C@@H:13]([CH3:17])[C:14]([OH:16])=O)[CH:8]=[N:7][C:6]=2[N:5]([CH3:18])[C:4]1=[O:19].[CH3:20][C@H:21]1[CH2:25][CH2:24][CH2:23][N:22]1[C:26]1[N:31]=[CH:30][C:29]([C:32]2[N:37]=[C:36]([NH2:38])[CH:35]=[N:34][CH:33]=2)=[CH:28][N:27]=1.C1C=NC2N(O)N=NC=2C=1.N1C=CC=CC=1.CC(C)N=C=NC(C)C>C(Cl)Cl>[CH3:2][N:3]1[C:11](=[O:12])[C:10]2[N:9]([C@@H:13]([CH3:17])[C:14]([NH:38][C:36]3[CH:35]=[N:34][CH:33]=[C:32]([C:29]4[CH:28]=[N:27][C:26]([N:22]5[CH2:23][CH2:24][CH2:25][C@@H:21]5[CH3:20])=[N:31][CH:30]=4)[N:37]=3)=[O:16])[CH:8]=[N:7][C:6]=2[N:5]([CH3:18])[C:4]1=[O:19]

Participants

7

Reactant 5

HCID 1049PyridineHCID 12734DiisopropylcarbodiimideHCID 181649HOAtHCID 86727124HCID 86727124, compoundHCID 86727126HCID 86727126, compound2×

Product 1

HCID 86727125HCID 86727125, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A flask was charged with (S)-2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propanoic acid hydrochloride (Intermediate 8) (8.96 g, 31.0 mmol), (S)-6-(2-(2-methylpyrrolidin-1-yl)pyrimidin-5-yl)pyrazin-2-amine (7.23 g, 28.2 mmol), HOAt (3.84 g, 28.2 mmol), nitrogen, DCM (141 ml) and stirred at room temperature. The suspension was cooled to 0° C. followed by addition of pyridine (4.60 ml, 56.4 mmol), then DIC (6.59 ml, 42.3 mmol). The reaction was removed from ice bath immediately after addition of DIC was complete. The reaction was complete after 7.5 hours. The reaction mixture was diluted with 100 mL DCM. The organic layer was washed with 0.5 M HCl aq. (2×20 mL). The resulting organic layer was washed with water, brine, dried over MgSO4, filtered and concentrated. The resulting DCM filtrate was slowly added dropwise to 300 mL of stirred hexanes at room temperature. The resulting solids were collected via vacuum filtration with aide of hexanes and dried on on frit filter overnight to afford off-white solids (6.5 g, 13.25 mmol, 47.0% yield, 93% ee). ESI-MS (EI+, m/z): 491.33, 1H NMR (DMSO-d6) δ: 11.35 (s, 1H), 9.10 (s, 1H), 9.05 (s, 2H), 8.91 (s, 1H), 8.36 (s, 1H), 5.85 (d, J=7.2 Hz, 1H), 4.30 (s, 1H), 3.59 (d, J=27.6 Hz, 2H), 3.46 (s, 3H), 3.19 (s, 3H), 2.08 (s, 3H), 1.95 (s, 1H), 1.88 (d, J=7.3 Hz, 3H), 1.72 (s, 1H), 1.24 (d, J=6.3 Hz, 3H)

Workup

  1. temperatureThe suspension was cooled to 0° C.
  2. customThe reaction was removed from ice bath
  3. additionimmediately after addition of DIC
  4. additionThe reaction mixture was diluted with 100 mL DCM
  5. washThe organic layer was washed with 0.5 M HCl aq. (2×20 mL)
  6. washThe resulting organic layer was washed with water, brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionThe resulting DCM filtrate was slowly added dropwise to 300 mL of stirred hexanes at room temperature
  11. filtrationThe resulting solids were collected via vacuum filtration with aide of hexanes
  12. customdried on on frit
  13. filtrationfilter overnight
  14. customto afford off-white solids (6.5 g, 13.25 mmol, 47.0% yield, 93% ee)

Sources & evidence

ORD record
ord-b829e31eb8d244a882f19080e544bc45
Source dataset
uspto-grants-2016_07
Patent number
US09394308B2

Reaction notes

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