1,2-Dichloroethane → HCID 46896394, compound

HRID 880395Notes

Reaction equation

HRID 880395 reaction equation
[CH3:1]CN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH:24]1([N:28]2[CH2:33][CH2:32][N:31]([C:34]([C@@H:36]3[CH2:38][C@H:37]3[C:39]3[CH:47]=[CH:46][C:42]([C:43]([NH2:45])=[O:44])=[CH:41][CH:40]=3)=[O:35])[CH2:30][C@H:29]2[CH3:48])[CH2:27][CH2:26][CH2:25]1>CN(C=O)C>[CH:24]1([N:28]2[CH2:33][CH2:32][N:31]([C:34]([C@@H:36]3[CH2:38][C@H:37]3[C:39]3[CH:40]=[CH:41][C:42]([C:43]([NH2:45])=[O:44])=[CH:46][CH:47]=3)=[O:35])[CH2:30][C:29]2([CH3:1])[CH3:48])[CH2:25][CH2:26][CH2:27]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 46896296HCID 46896296, compound

Product 1

HCID 46896394HCID 46896394, compoundYield 30.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Intermediate 14 (282 mg, 1.38 mmol) was dissolved in DMF (15 mL). DIPEA (1.201 mL, 6.88 mmol) was added, followed by HOBT (279 mg, 2.06 mmol), EDC (395 mg, 2.06 mmol) and Intermediate 2 (278 mg, 1.65 mmol). The reaction mixture was stirred at rt for 2 h and concentrated under reduced pressure. The residue was redissolved in DCM, washed with sat NaHCO3, dried over MgSO4, filtered and concentrated under reduced pressure to give 632 mg of crude as an orange oil. The crude material was purified on preparative HPLC UV using the long high pH shallow gradient method (Mobile phase: 20-40% B; A: H2O with 10 mM NH4CO3 and 0.375% NH4OH v/v, B: CH3CN, 30 min run) on XBridge Prep C18 OBD, 50×250 mm, 10μ, Waters reverse phase column, providing 151 mg title compound (30.9%) as a solid (enantiomeric mixture). 1H NMR (400 MHz, CD3OD) δ ppm 1.01 (s, 2H) 1.08 (s, 4H) 1.34-1.43 (m, 1H) 1.55-1.70 (m, 4H) 1.96-2.12 (m, 5H) 2.25-2.37 (m, 1H) 2.40-2.48 (m, 1H) 2.61 (br. s., 2H) 3.45 (br. s., 2H) 3.75 (br. s., 1H) 7.26 (dd, J=8.20, 5.08 Hz, 2H) 7.80 (dd, J=8.40, 2.93 Hz, 2H); HRMS m/z calcd for C21H30N3O2 356.23325 [M+H]+, found 356.23286.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was redissolved in DCM
  3. washwashed
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give 632 mg of crude as an orange oil
  8. customThe crude material was purified on preparative HPLC UV
  9. customCH3CN, 30 min

Sources & evidence

ORD record
ord-86eeb6793d08483cb930459d950e60a3
Source dataset
uspto-grants-2015_03
Patent number
US08993577B2

Reaction notes

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