Sodium hydride → HCID 59149777, compound

HRID 1675083Notes

Reaction equation

HRID 1675083 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:19]=[CH:20][C:21]4[N:22]([C:24]([C:27]([F:30])([F:29])[F:28])=[N:25][N:26]=4)[N:23]=3)[CH2:14][CH2:13]2)=[CH:4]1.Cl.Cl[CH2:33][CH2:34][N:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1>CN(C=O)C>[N:35]1([CH2:34][CH2:33][N:3]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([CH:12]3[CH2:13][CH2:14][N:15]([C:18]4[CH:19]=[CH:20][C:21]5[N:22]([C:24]([C:27]([F:30])([F:29])[F:28])=[N:25][N:26]=5)[N:23]=4)[CH2:16][CH2:17]3)=[CH:4]2)[CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 25493920HCID 25493920, compound

Product 1

HCID 59149777HCID 59149777, compoundYield 27.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% dispersion in oil, 31 mg, 0.75 mmol) was added to 6-[4-(1H-indol-3-yl)piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (obtained as described in Example 507) (150 mg, 0.39 mmol) suspended in DMF (2 mL) at 0° C. under nitrogen. The resulting mixture was stirred at 0° C. for 30 minutes, then 1-(2-chloroethyl)pyrrolidine hydrochloride (72.6 mg, 0.43 mmol) in DMF (1 mL) was added. The resulting mixture was stirred at ambient temperature for 18 hours. The reaction mixture was evaporated to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to give 6-[4-[1-(2-pyrrolidin-1-ylethyl)-1H-indol-3-yl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (52.0 mg, 27.7%) as a white solid.

Workup

  1. stirringThe resulting mixture was stirred at ambient temperature for 18 hours
  2. customThe reaction mixture was evaporated
  3. customto afford crude product
  4. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  5. additionFractions containing the desired compound
  6. customwere evaporated to dryness

Sources & evidence

ORD record
ord-a0027925951a430d8b5645ae6aa7b2fa
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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