2-Propanethiol → HCID 57411213, compound

HRID 1502333Notes

Reaction equation

HRID 1502333 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[CH3:18][CH:19]([SH:21])[CH3:20].CC(C)([O-])C.[Na+]>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:19]([S:21][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1)([CH3:20])[CH3:18]

Participants

8

Reactant 3

HCID 63642-PropanethiolHCID 23676156Sodium t-butoxideHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 57411213HCID 57411213, compoundYield 19%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (725 mg, 2.5 mmol), propane-2-thiol (281 mg, 3.75 mmol), palladium(II) acetate (11.2 mg, 0.05 mmol), 1,1′-bis(diphenylphosphino)ferrocene (33.4 mg, 0.06 mmol) and sodium tert-butoxide (480 mg, 5.0 mmol) in dioxane (5 mL) was stirred at 100° C. overnight under nitrogen. The reaction mixture was diluted with ethyl acetate (10 mL) and filtered. The solid was extracted with ethyl acetate (20 mL×3). The organic layer was combined, dried with sodium sulfate, filtered and concentrated in vacuo. It was purified by prep-HPLC to give the product (130 mg, 19%). LCMS (ESI): RT (Min)=1.285, M+H =286.9, method=A; 1H NMR (MeOD-d4, 400 MHz): δ 8.96 (s, 1H), 8.36 (s, 1H), 7.96 (t, J=0.8 Hz, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.65 (dd, J=2.0, 8.8 Hz, 1H), 3.59-3.55 (m, 1H), 1.93-1.91 (m, 1H), 1.33 (d, J=6.4 Hz, 6H), 1.01-0.99 (m, 2H), 0.91-0.89 (m, 2H).

Workup

  1. filtrationfiltered
  2. extractionThe solid was extracted with ethyl acetate (20 mL×3)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customIt was purified by prep-HPLC

Sources & evidence

ORD record
ord-a9a51c159e814cacbd5fb4558f000e7e
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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