Acetic Acid → HCID 58094958, compound

HRID 2402468Notes

Reaction equation

HRID 2402468 reaction equation
C([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:13][C:12]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([N:20]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:21](=[O:23])[CH3:22])[CH:15]=2)=[C:11]([C:33]#[N:34])[C:10]=1[C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=1[Cl:42])C=C.C(O)(=O)C.C(Cl)Cl.C1([SiH3])C=CC=CC=1>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.C(Cl)Cl>[C:33]([C:11]1[C:10]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=2[Cl:42])=[C:9]([C:5]2[NH:6][CH:7]=[CH:8][N:4]=2)[S:13][C:12]=1[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([N:20]([CH2:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)[C:21](=[O:23])[CH3:22])[CH:15]=1)#[N:34]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 12752PhenylsilaneHCID 58095248HCID 58095248, compound

Product 1

HCID 58094958HCID 58094958, compoundYield 50.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21226138Dichloromethane ethylacetateSolvent

Conditions

Temperature
40 °C

Procedure

To the solution of N-{4-[5-(1-allyl-1H-imidazol-2-yl)-3-cyano-4-(2,4-dichlorophenyl)-2-thienyl]pyridin-2-yl}-N-(4-methoxybenzyl)acetamide (1.32 g, 1.61 mmol) and Tetrakis(triphenylphosphine)palladium(0) (93.1 mg, 0.0805 mmol) in Acetic acid (15 mL, 260 mmol) and Methylene chloride (30 mL, 500 mmol) under N2 atmosphere was added dropwise PHENYLSILANE (1.10 mL, 8.92 mmol). The mixture was stirred at 40° C. for 2 hours. The solvent was removed in rotavapor then the residue was dried in high vacuum to give a residue. The residue was chromatographed in silica column using 7N NH3-MeOH/DCM (1/99, ˜1 L), then EtOAc/DCM (30/70 to 60/40) to give an impure product. The second chromatograph using EtOAc/DCM (30/70 to 80/20) gave a pure product (0.469 g, yield 50.7%). LCMS: (AA) ES+, 574, 576; ES−, 572, 574. 1H NMR (400 MHz, d1-chloroform) δ: 8.60-8.62 (d, J=5.27 Hz, 1H), 7.71 (d, J=2.00 Hz, 1H), 7.63 (s, br, 1H), 7.55-7.57 (dd, J=5.27, 1.76 Hz, 1H), 7.50-7.52 (dd, J=8.28, 2.01 Hz, 1H), 7.40-7.42 (d, J=8.28 Hz, 1H). 7.18-7.20 (d, J=8.78 Hz, 2H), 7.07 (m, 2H), 6.80-6.82 (d, J=8.78 Hz, 2H), 5.14 (s, 2H), 3.76 (s, 3H), 2.19 (s, 3H).

Workup

  1. customThe solvent was removed in rotavapor
  2. customthe residue was dried in high vacuum
  3. customto give a residue
  4. customThe residue was chromatographed in silica column
  5. customEtOAc/DCM (30/70 to 60/40) to give an impure product

Sources & evidence

ORD record
ord-c3334872083e48f6aad47df9cc144d6d
Source dataset
uspto-grants-2014_08
Patent number
US08796314B2

Reaction notes

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