Sodium Carbonate → 4-Amino-2-[5-(cyano-vinyl)-thiophen-3-yl]-thieno[3,2-c]pyridine-7-carboxylic acid amide

HRID 1868315Notes

Reaction equation

HRID 1868315 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]#[N:10])[S:5][CH:6]=1.[K].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.[NH2:30][C:31]1[C:36]2[CH:37]=[C:38](Br)[S:39][C:35]=2[C:34]([C:41]([NH2:43])=[O:42])=[CH:33][N:32]=1.C([O-])([O-])=O.[Na+].[Na+]>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.CN(C=O)C>[NH2:30][C:31]1[C:36]2[CH:37]=[C:38]([C:2]3[CH:3]=[C:4]([CH:7]=[CH:8][C:9]#[N:10])[S:5][CH:6]=3)[S:39][C:35]=2[C:34]([C:41]([NH2:43])=[O:42])=[CH:33][N:32]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 2733548Bis(pinacolato)diboraneHCID 5462222PotassiumHCID 588407134-Amino-2-Bromothieno[3,2-C]pyridine-7-CarboxamideHCID 690694473-(4-Bromo-thiophen-2-yl)-acrylonitrile

Product 1

HCID 690707884-Amino-2-[5-(cyano-vinyl)-thiophen-3-yl]-thieno[3,2-c]pyridine-7-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(4-bromo-thiophen-2-yl)-acrylonitrile 76 (0.33 g, 1.55 mmol), potassium acatete (0.47 g, 4.74 mmol), bis(pinacolato)diboron (0.84 g, 3.3 mmol), Pd(PPh3)4 (0.12 g, 0.1 mmol), and DMF (11 mL) was heated at 100° C. under nitrogen for 1 h. 4-Amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide 17 (0.28 g, 1.0 mmol), 2 M aqueous Na2CO3 solution (3.6 mL), and Pd(PPh3)4 (0.12 g, 0.11 mmol) were added. The reaction mixture was then heated at 100° C. under nitrogen until completion of the reaction (approx. 1 h), cooled to room temperature and concentrated in vacuo to approx. half volume. The mixture was diluted with water (20 mL) and the precipitate of 77 that formed was collected by filtration, washed with MeOH, and dried. 4-amino-2-[5-(cyano-vinyl)-thiophen-3-yl]-thieno[3,2-c]pyridine-7-carboxylic acid amide 77 was then dissolved in pyridine (5 mL) and EtOH (1 mL). To the resulting solution was added NaBH4 (0.16 g, 4.1 mmol). The solution was then heated at 100° C. until completion of the reaction (approx. 2 h) and then concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: 80% of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2). The major fractions were combined and concentrated to give 78 (0.12 g) as a pale-yellow solid. 1H NMR (400 MHz, d6-DMSO) δ: 8.48 (s, 1H), 7.90 (br.s, 1H), 7.86 (s, 1H), 7.65 (d, J=1.4 Hz, 1H), 7.31 (s, 1H), 7.26 (br s, 1H), 7.12 (s, 2H), 3.17 (t, 2H), 2.92 (t, 2H). MS (EI) m/z (M+H+) 329 and (M+Na+) 351.

Workup

  1. temperatureThe reaction mixture was then heated at 100° C. under nitrogen until completion of the reaction (approx. 1 h)
  2. temperaturecooled to room temperature
  3. concentrationconcentrated in vacuo to approx. half volume
  4. additionThe mixture was diluted with water (20 mL)

Sources & evidence

ORD record
ord-eb76aa1ee183424d8d848e9d323237bc
Source dataset
uspto-grants-2009_12
Patent number
US07635695B2

Reaction notes

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