Potassium Fluoride → Tert-butyl (2e)-3-(4-amino-3-bromothieno[3,2-c]pyridin-7-yl)-2-propenylcarbamate

HRID 1270861Notes

Reaction equation

HRID 1270861 reaction equation
[Br:1][C:2]1[C:6]2[C:7]([NH2:12])=[N:8][CH:9]=[C:10](I)[C:5]=2[S:4][CH:3]=1.C([Sn](CCCC)(CCCC)/[CH:18]=[CH:19]/[CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])CCC.[F-].[K+]>C1(C)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>[NH2:12][C:7]1[C:6]2[C:2]([Br:1])=[CH:3][S:4][C:5]=2[C:10](/[CH:18]=[CH:19]/[CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:9][N:8]=1

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 14934033tert-butyl N-((2E)-3-(tributylstannyl)prop-2-en-1-yl)carbamateHCID 184507913-Bromo-7-iodothieno[3,2-C]pyridin-4-amine

Product 1

HCID 131726331Tert-butyl (2e)-3-(4-amino-3-bromothieno[3,2-c]pyridin-7-yl)-2-propenylcarbamate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of Example 21A (1.0 g, 2.8 mmol), tert-butyl (2E)-3-(tributylstannyl)-2-propenylcarbamate (prepared according to the procedure described in Synthesis, 1991, (12), 1201, 1.5 g, 3.36 mmol), and potassium flouride (195 mg, 3.36 mmol) in toluene (10 mL) was degassed, treated with Pd(PPh3)4 (194 mg, 0.17 mmol), degassed, and heated to 110° C. for 14 hours under a nitrogen atmosphere. The mixture was concentrated and purified by flash chromatography on silica gel with dichloromethane/ethyl acetate (6:4) to provide the desired product (1.3 g, 3.36 mmol). 1H NMR (DMSO-d6, 400 MHz) δ 7.93 (s, 1H), 7.35 (s, 1H), 6.55 (d, 1H), 6.21 (dt, 1H), 5.81 (br s, 2H), 4.73 (br s, 1H), 3.98 (s, 2H), 1.48 (s, 9H); reverse phase HPLC (5% to 95% acetonitrile over 25 minutes, 1 mL/min, 254 nm, hypersil HS 100 Å, C18, 5 μm, 250×4.6 column) Rt=15.5 minutes; MS m/e 385.1.

Workup

  1. customwas degassed
  2. customdegassed
  3. concentrationThe mixture was concentrated
  4. custompurified by flash chromatography on silica gel with dichloromethane/ethyl acetate (6:4)

Sources & evidence

ORD record
ord-f5a87f9f47774eec8e25f483e3492c60
Source dataset
uspto-grants-2007_04
Patent number
US07202363B2

Reaction notes

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