Water → HCID 24986682, compound

HRID 1946952Notes

Reaction equation

HRID 1946952 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([N:10]1[C:16]2[CH:17]=[C:18](B3OC(C)(C)C(C)(C)O3)[S:19][C:15]=2[C:14](=[O:29])[NH:13][CH2:12][CH2:11]1)[CH3:9].I[C:31]1[N:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]2=[N:33][CH:32]=1.C([O-])([O-])=O.[K+].[K+].O>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([N:10]1[C:16]2[CH:17]=[C:18]([C:31]3[N:35]4[CH:36]=[CH:37][CH:38]=[CH:39][C:34]4=[N:33][CH:32]=3)[S:19][C:15]=2[C:14](=[O:29])[NH:13][CH2:12][CH2:11]1)[CH3:9]

Participants

9

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 107527743-Iodoimidazo[1,2-a]pyridineHCID 58074319HCID 58074319, compound

Product 1

HCID 24986682HCID 24986682, compoundYield 35.6%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

1-[1-(2-Chloro-phenyl)-ethyl]-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2,3,4-tetrahydro-thieno[3,2-e][1,4]diazepin-5-one (251 mg, 0.58 mmol, 1.3 Eq), 3-iodo-imidazo[1,2-a]pyridine (109 mg, 0.45 mmol, 1.0 Eq) and Pd(PPh3)4 (52 mg, 0.045 mmol, 0.1 Eq) were dissolved in toluene (1.6 mL) and EtOH (0.4 mL). 2M K2CO3 (0.45 mL, 0.89 mmol, 2.0 Eq) was added and the reaction heated at 140° C. for 15 minutes under microwave conditions. Water (10 mL) and EtOAc (15 mL) was added and the layers separated. The aqueous layer was extracted with EtOAc (3×10 mL) and the combined organic layers washed with brine (15 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography to give the title compound as a pale yellow solid (66 mg, 0.16 mmol, 35%); 1H NMR (DMSO D6) 1.57 (3H, d), 2.92-3.00 (1H, m), 3.10-3.18 (1H, m), 3.29-3.33 (2H, m), 5.51 (1H, q), 7.12 (1H, t), 7.36-7.46 (4H, m), 7.52 (1H, d), 7.59 (1H, d), 7.69-7.75 (2H, m), 7.95 (1H, s), 8.62 (1H, d); LC/MS M+1 (obs.) 423.1, LC/MS M−1 (obs.) 421.3.

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
  3. washthe combined organic layers washed with brine (15 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by chromatography

Sources & evidence

ORD record
ord-9714c7575a464deb8e4a4a4a71fe6eda
Source dataset
uspto-grants-2013_03
Patent number
US08399458B2

Reaction notes

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