Cesium carbonate → HCID 67387473, compound

HRID 1472418Notes

Reaction equation

HRID 1472418 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.Br[C:11]1[CH:12]=[C:13]2[C@@:24]3([N:29]=[C:28]([NH2:30])[CH2:27][O:26][CH2:25]3)[C:23]3[C:18](=[CH:19][CH:20]=[C:21](I)[CH:22]=3)[O:17][C:14]2=[N:15][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:38][C:39]([CH3:43])([CH3:42])[C:40]#[CH:41].C(=O)([O-])[O-].[Cs+].[Cs+]>CC1OCCC1.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.O.O1CCOCC1>[CH3:38][C:39]([CH3:43])([CH3:42])[C:40]#[C:41][C:11]1[CH:12]=[C:13]2[C@@:24]3([N:29]=[C:28]([NH2:30])[CH2:27][O:26][CH2:25]3)[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[CH:22]=3)[O:17][C:14]2=[N:15][CH:16]=1

Participants

10

Reactant 5

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 135123,3-Dimethyl-1-butyneHCID 27343783-Pyridinylboronic acid2×HCID 58465904(S)-3-bromo-7-iodo-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amine

Product 1

HCID 67387473HCID 67387473, compoundYield 20.02%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 73012-MethyltetrahydrofuranSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with pyridin-3-ylboronic acid (0.027 g, 0.222 mmol), PdCl2(dppf)-CH2Cl2-adduct (8.65 mg, 10.59 μmol), (S)-3-bromo-7-iodo-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.100 g, 0.212 mmol), and potassium carbonate (0.117 g, 0.847 mmol). Dioxane (5 mL) and water (0.5 mL) were added. The vial was flushed with argon, and heated to 100° C. for 1 hour. An additional portion of pyridin-3-ylboronic acid (0.027 g, 0.222 mmol) was added, and the reaction mixture was heated to 100° C. for an additional hour. The reaction mixture was diluted with 2-MeTHF, dried over MgSO4 and concentrated under reduced pressure. The crude residue was used without purification. Step 2: The crude residue from step 1 was dissolved in 2 mL DMF, treated with 3,3-dimethyl-1-butyne (0.130 mL, 1.059 mmol), cesium carbonate (0.345 g, 1.059 mmol), and tBu-XPhos palladacycle (7.27 mg, 10.59 μmol). The reaction mixture was capped under argon, and was heated to 90° C. for 2 hours. The reaction mixture was then diluted with 2-MeTHF and washed with water. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography [0-100% (95:5 EtOAc/MeOH)/DCM] gave (S)-3-(3,3-dimethylbut-1-ynyl)-7-(pyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.018 g, 0.042 mmol, 20.02% yield) as a grey solid. [M+H]+=425.0

Workup

  1. customThe vial was flushed with argon
  2. temperaturethe reaction mixture was heated to 100° C. for an additional hour
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was used without purification
  6. dissolutionStep 2: The crude residue from step 1 was dissolved in 2 mL DMF
  7. customThe reaction mixture was capped under argon
  8. temperaturewas heated to 90° C. for 2 hours
  9. washwashed with water
  10. dry with materialThe organics were dried over MgSO4
  11. concentrationconcentrated
  12. customPurification of the crude residue by column chromatography [0-100% (95:5 EtOAc/MeOH)/DCM]

Sources & evidence

ORD record
ord-d1f128194511482f97de81bb8cfd2e0a
Source dataset
uspto-grants-2015_04
Patent number
US09012446B2

Reaction notes

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