Dichloromethane → [5-[2-(4-Ethoxycarbonyl-4-methyl-1-piperidyl)pyrimidin-5-yl]-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-7-yl]boronic acid

HRID 712183Notes

Reaction equation

HRID 712183 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([N:11]3[CH2:16][N:15]([CH3:17])[CH2:14][N:13]([CH2:18][CH3:19])[C:12]3=[O:20])=[N:7][C:6]=2[CH:5]=[C:4]([C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:32][CH2:31][C:30]([CH3:38])([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:29][CH2:28]3)=[N:25][CH:26]=2)[CH:3]=1.[B:39]1(B2OCC(C)(C)CO2)[O:44]CC(C)(C)C[O:40]1.C(Cl)Cl.C([O-])(=O)C.[K+]>CCCCCC.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].C1(C)C=CC=CC=1>[CH2:36]([O:35][C:33]([C:30]1([CH3:38])[CH2:31][CH2:32][N:27]([C:24]2[N:23]=[CH:22][C:21]([C:4]3[CH:3]=[C:2]([B:39]([OH:44])[OH:40])[C:10]4[S:9][C:8]([N:11]5[CH2:16][N:15]([CH3:17])[CH2:14][N:13]([CH2:18][CH3:19])[C:12]5=[O:20])=[N:7][C:6]=4[CH:5]=3)=[CH:26][N:25]=2)[CH2:28][CH2:29]1)=[O:34])[CH3:37]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 66977053Ethyl 1-[5-[7-bromo-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Product 1

HCID 66976948[5-[2-(4-Ethoxycarbonyl-4-methyl-1-piperidyl)pyrimidin-5-yl]-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-7-yl]boronic acidYield 125.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolventHCID 8058HexaneSolvent

Conditions

Temperature
130 °C

Procedure

Ethyl 1-[5-[7-bromo-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (100 mg, 0.166 mmol), bis(neopentyl glycolato)diboron (75 mg, 0.33 mmol), Pd(dppf)Cl2.DCM (14 mg, 0.017 mmol), potassium acetate (49 mg, 0.50 mmol) and toluene (2 mL) were sealed in a microwave reaction vial under argon and heated at 130° C. for 40 min. The reaction mixture was diluted with n-hexane (10 mL) before being filtered to remove particulate palladium residues. The filtrate was concentrated to obtain desired product (118 mg, light brown solid). 1H NMR (MeOD) δ 8.63 (s, 2H), 7.91 (d, J=1.9 Hz, 1H), 7.82 (d, J=1.8 Hz, 1H), 5.20 (s, 2H), 4.44-4.34 (m, 4H), 4.21 (q, J=7.1 Hz, 2H), 3.50-3.42 (m, 2H), 3.33-3.28 (m, 2H, obscured by solvent), 2.65 (s, 3H), 2.21-2.13 (m, 2H), 1.69-1.38 (m, 2H), 1.33-1.19 (m, 9H). m/z [M+H]+ 568.1.

Workup

  1. filtrationbefore being filtered
  2. customto remove particulate palladium residues
  3. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-9d358b7999e54fb3828c6e5d0f7e5a57
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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