Cesium carbonate → HCID 59369872, compound

HRID 1662089Notes

Reaction equation

HRID 1662089 reaction equation
Br[C:2]1[S:6][C:5]([CH3:7])=[N:4][C:3]=1[C:8]([N:10]1[CH2:15][C@@H:14]2[C@@H:12]([CH2:13]2)[C@H:11]1[CH2:16][NH:17][C:18]1[O:19][C:20]2[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=2[N:22]=1)=[O:9].[C:27]1([CH3:36])[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.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]>[CH3:7][C:5]1[S:6][C:2]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[CH3:36])=[C:3]([C:8]([N:10]2[CH2:15][C@@H:14]3[C@@H:12]([CH2:13]3)[C@H:11]2[CH2:16][NH:17][C:18]2[O:19][C:20]3[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=3[N:22]=2)=[O:9])[N:4]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27332672-Methylphenyl boronic acidHCID 59369807HCID 59369807, compound

Product 1

HCID 59369872HCID 59369872, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of N-({(1R,2S,5S)-3-[(5-bromo-2-methyl-1,3-thiazol-4-yl)carbonyl]-3-azabicyclo[3.1.0]hex-2-yl}methyl)-1,3-benzoxazol-2-amine (0.010 g, 0.023 mmol) and 2-tolylboronic acid (0.012 g, 0.092 mmol) in DMF (0.25 mL) was added 1M aqueous cesium carbonate (0.092 mL, 0.092 mmol) and PdCl2(dppf) (0.0016 g, 0.0023 mmol) and heated in a microwave to 130° C. for 10 minutes. The system was cooled to room temperature, extracted with EtOAc, washed with water, dried over sodium sulfate and concentrated. The crude reaction mixture was then purified using reverse phase conditions (5%→60% 0.1% TFA in water: 0.1% TFA in acetonitrile) followed by free basing with saturated sodium carbonate to afford the title compound (2-2) as a bone powder. 1H NMR (500 MHz, CDCl3) δ 7.35 (m, 1H), 7.19-7.34 (m, 5H), 7.14 (m, 1H), 7.02 (m, 1H), 4.29 (m, 1H), 3.98 (m, 1H), 3.52 (m, 2H), 3.39 (m, 1H), 2.75 (s, 3H), 2.32 (s, 3H), 1.81 (m, 1H), 1.44 (m, 1H), 0.882 (m, 1H), 0.548 (m, 1H). HRMS [M+H] C25H24N4O2S1 calc'd 445.1693, found 445.1679.

Workup

  1. temperatureThe system was cooled to room temperature
  2. extractionextracted with EtOAc
  3. washwashed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude reaction mixture
  7. customwas then purified

Sources & evidence

ORD record
ord-e0283edfc04a451d97525f1b5b385476
Source dataset
uspto-grants-2011_10
Patent number
US08030495B2

Reaction notes

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