Sodium Carbonate → HCID 86345854, compound

HRID 1772736Notes

Reaction equation

HRID 1772736 reaction equation
Br[C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH2:12][C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[N:10]=[C:6]2[C:5]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[N:4][CH:3]=1.[CH3:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][C:37]1[CH:42]=[CH:41][C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH:38]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][C:37]1[CH:38]=[CH:39][C:40]([C:2]2[N:7]3[CH:8]=[C:9]([CH2:11][CH2:12][C:13]4[CH:22]=[CH:21][C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[N:14]=4)[N:10]=[C:6]3[C:5]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[N:4][CH:3]=2)=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 91641346HCID 91641346, compoundHCID 1177278954-(5-Bromo-2-(2-(quinolin-2-yl)ethyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

Product 1

HCID 86345854HCID 86345854, compound

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of compound 3a (100 mg, 0.228 mmol), compound 85b (88.2 mg, 0.274 mmol), PdCl2(dppf)-DCM (5.6 mg, 0.0068 mmol), and Argon-degassed aqueous 2M Na2CO3 (0.570 mL, 1.14 mmol) in Argon-degassed 1,4-dioxane (4 mL) was further degassed with Argon for 2 min and then stirred at 90° C. for 5 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to a brown oil which was purified by flash column chromatography on silica gel (0-100% EtOAc-heptane, followed by 100% EtOAc) to afford a colorless resin. The residue obtained was further purified by flash column chromatography (100% EtOAc, followed by 0-10% MeOH-EtOAc) to afford a colorless oil, which was triturated with EtOAc-heptane (1:3) and concentrated under reduced pressure to give the title compound 31 as an off-white crystalline solid. 1H-NMR (CDCl3; 400 MHz): δ (ppm) 8.01-8.08 (m, 2H), 7.79 (d, J=8.1 Hz, 1H), 7.67-7.73 (m, 1H), 7.48-7.54 (m, 1H), 7.30-7.38 (m, 4H), 7.24 (s, 1H), 6.98 (d, J=8.6 Hz, 2H), 4.16-4.23 (m, 6H), 3.91 (t, J=4.8 Hz, 2H), 3.82-3.86 (m, 4H), 3.73-3.78 (m, 2H), 3.59-3.63 (m, 2H), 3.41-3.42 (m, 3H), 3.38-3.44 (m, 2H), 3.27-3.33 (m, 2H); Mass spectrum (LCMS, ESI pos.): Calcd. for C32H35N5O4, 554.3 (M+H). found 554.5.

Workup

  1. customdegassed 1,4-dioxane (4 mL)
  2. customwas further degassed with Argon for 2 min
  3. temperatureAfter cooling to room temperature
  4. concentrationthe reaction mixture was concentrated under reduced pressure to a brown oil which
  5. customwas purified by flash column chromatography on silica gel (0-100% EtOAc-heptane, followed by 100% EtOAc)
  6. customto afford a colorless resin
  7. customThe residue obtained
  8. customwas further purified by flash column chromatography (100% EtOAc, followed by 0-10% MeOH-EtOAc)
  9. customto afford a colorless oil, which
  10. customwas triturated with EtOAc-heptane (1:3)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1121a388ec2c47dea1ca52b0888cda20
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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