Water → HCID 11705623, compound

HRID 601551Notes

Reaction equation

HRID 601551 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][C:11]3[N:14]=[C:15]([C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=4)[S:16][C:10]=3[C:9]2=[O:24])=[CH:4][C:3]=1[O:25][CH3:26].[CH2:27]([N:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1)[C:28]#[CH:29].C(N(CC)CC)C.O>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([C:15]2[S:16][C:10]3[C:9](=[O:24])[N:8]([C:5]4[CH:6]=[CH:7][C:2]([C:29]#[C:28][CH2:27][N:30]5[CH2:34][CH2:33][CH2:32][CH2:31]5)=[C:3]([O:25][CH3:26])[CH:4]=4)[CH2:13][CH2:12][C:11]=3[N:14]=2)=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 2996161-(Prop-2-yn-1-yl)pyrrolidineHCID 57501783HCID 57501783, compound

Product 1

HCID 11705623HCID 11705623, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Treat a suspension of 5-(4-bromo-3-methoxy-phenyl)-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (0.25 mg, 0.56 mmol), 1-prop-2-ynyl-pyrrolidine (0.12 g, 1.10 mmol), dichlorobis(triphenylphosphine)palladium (II) (12.0 mg, 0.02 mmol), triethylamine (0.5 mL) in DMF with CuI (4.0 mg, 0.02 mmol). Stir at 80° C. under nitrogen for 2 days. Dilute the reaction with water and extract with CH2Cl2 (2×). Dry, filter, and concentrate the organic solution and purify the crude material by flash chromatography, using a gradient of 0-10% MeOH in CH2Cl2 to give the title compound (30.0 mg, 12%). MS (ES+) 478.0 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 7.89 (d, 2H, J=8.8 Hz), 7.40 (m, 3H), 6.95 (d, 1H, J=2.2 Hz), 6.82 (dd, 1H, J=8.1, 2.0 Hz), 4.10 (t, 2H, J=6.8 Hz), 3.84 (m, 5H), 3.26 (t, 2H, J=6.8 Hz), 2.88 (m, 4H), 1.89 (m, 4H).

Workup

  1. additionTreat
  2. additionDilute
  3. extractionextract with CH2Cl2 (2×)
  4. customDry
  5. filtrationfilter
  6. concentrationconcentrate the organic solution
  7. custompurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-51cb56cc265a4e0f8b55daadc955b608
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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