3-(Pyrrolidin-2-yl)pyridine → HCID 10182731, compound

HRID 966477Notes

Reaction equation

HRID 966477 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][CH2:22]Cl)[CH:18]=2)[NH:13][C:12]=1[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:25]1[CH2:29][CH2:28][CH2:27][CH:26]1[C:30]1[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=1>C(#N)C.C(Cl)Cl>[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][CH2:22][N:25]3[CH2:29][CH2:28][CH2:27][CH:26]3[C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)[CH:18]=2)[NH:13][C:12]=1[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 4123-(Pyrrolidin-2-yl)pyridineHCID 23393871HCID 23393871, compound

Product 1

HCID 10182731HCID 10182731, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(2-chloro-ethoxy)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (Example 1, Step A, 0.400 g, 1.16 mmol), 3-pyrrolidin-2-yl-pyridine (0.345 mL, 2.33 mmol), K2CO2 (0.322 g, 2.33 mmol), and KI (0.019 g, 0.116 mmol) in 23 mL of acetonitrile was heated at reflux for 24 hours. The reaction mixture was cooled to room temperature, diluted with CH2Cl2 (50 mL) and washed with water (2×20 mL). The organic layer was dried over MgSO4 and concentrated to give a brown oil. The product was purified by flash column chromatography on silica gel (3% methanol:CH2Cl2) and triturated with diethyl ether/hexanes/CH2Cl2 to give 0.120 g (23.0%) of a light yellow solid: mp 126-127° C.; IR (KBr)3036, 2962, 2793, 1693, 1594, 1454, 1168, 1077 cm−1; 1HNMR (400 MHz, DMSO-d6) δ 1.40-1.52 (m, 1H, NCHCH2CH2CH2), 1.70-1.85 (m, 2H, NCHCH2CH2CH2 & NCHCH2CH2CH2), 2.10-2.18 (m, 1H, NCHCH2CH2CH2), 2.29-2.31 (m, 1H, NCHCH2CH2CH2),2.34-2.42 (m, 1H, NCHCH2CH2CH2), 2.46 (s, 3H, CCH3), 2.71 (t, J=6.35 Hz, 2H, OCH2CH2), 3.38-3.42 (m, 1H, NCHCH2CH2CH2), 3.82 (t, J=5.62 Hz, 2H, OCH2CH2), 5.26 (s, 2H, OCH2Ar), 6.64 (dd, J=8.79, 2.44 Hz, 1H, ArH), 7.17 (t, J=8.55 Hz, 1H, ArH), 7.28 (t, J=7.08 Hz, 3H, ArH), 7.35 (t, J=7.33 Hz, 2H, ArH), 7.46 (d, J=7.81 Hz, 2H, ArH), 7.73 (d, J=7.81 Hz, 1H, ArH), 8.39-8.40 (m, 1H, ArH), 8.51 (s, 1H, ArH), 11.70 (s, 1H, NH); MS(APCI+): m/z 456.2 (MH+). Anal. Calcd for C28H29N3O3: C, 73.79; H, 6.42; N, 9.22. Found: C, 73.42; H, 6.45; N, 9.11.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 24 hours
  3. washwashed with water (2×20 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customto give a brown oil
  7. customThe product was purified by flash column chromatography on silica gel (3% methanol:CH2Cl2)
  8. customtriturated with diethyl ether/hexanes/CH2Cl2

Sources & evidence

ORD record
ord-0dcaf1d90d6b49adbbe730ec03c6171b
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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