Toluene → HCID 178504927, compound

HRID 1672471Notes

Reaction equation

HRID 1672471 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][CH2:14]1)[N:8]=[CH:7]2.C1(C)C=CC=CC=1.CCN(C(C)C)C(C)C.[CH3:36][S:37]([N:40]1[CH2:44][CH:43]=[CH:42][CH2:41]1)(=[O:39])=[O:38]>O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:36][S:37]([N:40]1[CH2:44][CH2:43][C:42]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[C:9]([NH:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][CH2:14]2)[N:8]=[CH:7]3)=[CH:41]1)(=[O:39])=[O:38]

Participants

7

Reactant 4

HCID 1140TolueneHCID 81531DiisopropylethylamineHCID 154087841-(Methanesulfonyl)-2,5-dihydro-1H-pyrroleHCID 178521594HCID 178521594, compound

Product 1

HCID 178504927HCID 178504927, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Procedure

To a shlenk tube was added trans-4-[(8-bromoquinazolin-2-yl)amino]cyclohexanol (322 mg, 1 mmol), followed by Pd(OAc)2 (48 mg, 0.2 mmol), (o-Tol)3P (60 mg, 0.2 mg), Ag2CO3 (192 mg, 0.7 mmol), toluene (8 mL) and iPr2NEt (516 mg, 4 mmol), followed by 1-(methylsulfonyl)-2,5-dihydro-1H-pyrrole (560 mg, 3.8 mmol). The mixture was refluxed overnight under Ar. TLC showed that several new spots were formed with small amount of starting material remaining. The reaction mixture was diluted with water (30 mL) and extracted with EtOAc (4×15 mL). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by chromatography (eluting with DCM, then DCM/EA 3/1, then DCM/EA=2/1) to afford the title compound (88 mg, 23%) as an off white solid. 1H-NMR (CDCl3, 400 MHz): δ 8.97 (s, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.55 (d, J=7.2 Hz, 1H), 7.21 (dd, J=8.8, 7.2 Hz, 1H), 6.60-6.58 (m, 1H), 5.51-5.49 (m, 1H), 5.22-5.19 (m, 1H), 5.16-5.11 (m, 1H), 4.36 (t, J=10.8 Hz, 1H), 3.99-3.94 (m, 1H), 3.58 (dd, J=10.8, 6.0 Hz, 1H), 2.85 (s, 3H), 2.30-2.24 (m, 2H), 2.12-2.08 (m, 2H), 1.41-1.26 (m, 4H).

Workup

  1. temperatureThe mixture was refluxed overnight under Ar
  2. customwere formed with small amount of starting material
  3. extractionextracted with EtOAc (4×15 mL)
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography (
  8. washeluting with DCM

Sources & evidence

ORD record
ord-86fb8801909a429080866896fe04835a
Source dataset
uspto-grants-2011_08
Patent number
US07998978B2

Reaction notes

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