Water → 5-[4-Methyl-4-(pyrrolidin-1-ylmethyl)-4,5-dihydro-1,3-oxazol-2-yl]-2-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridine

HRID 251458Notes

Reaction equation

HRID 251458 reaction equation
[CH3:1][C:2]1([CH:23]=O)[CH2:6][O:5][C:4]([C:7]2[CH:8]=[N:9][C:10]([O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:21][CH2:20][CH2:19][CH:18]3[CH3:22])=[CH:11][CH:12]=2)=[N:3]1.[NH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClC(Cl)C>[CH3:1][C:2]1([CH2:23][N:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)[CH2:6][O:5][C:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][N:17]3[CH2:21][CH2:20][CH2:19][CH:18]3[CH3:22])=[N:9][CH:8]=2)=[N:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 31268Pyrrolidine2×HCID 5049666Sodium triacetoxyborohydride2×HCID 119507254-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazole-4-carbaldehyde

Product 1

HCID 119498535-[4-Methyl-4-(pyrrolidin-1-ylmethyl)-4,5-dihydro-1,3-oxazol-2-yl]-2-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridineYield 25%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
22 °C

Procedure

A solution of 4-methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazole-4-carbaldehyde ax57 (273 mg, ca. 80% pure, ca. 0.66 mmol) in dichloroethane (4 ml) is treated with pyrrolidine (0.27 ml, 3.28 mmol) and sodium triacetoxyborohydride (0.35 g, 1.64 mmol), and the turbid solution is stirred at 22° C. overnight. Fresh pyrrolidine (0.145 ml, 1.64 mmol) and sodium triacetoxyborohydride (0.35 g, 1.64 mmol) are added and the solution is stirred for an additional 2 hours at room temperature. Water is then added and the mixture stirred vigorously for 5 minutes. Extraction is performed with dichloromethane until the organic extract does not contain significant UV-active spots. The combined organic layers are dried over sodium sulfate and concentrated to yield a brown oil. The product is purified by chromatography over silicagel (eluent: gradient 10 to 20% triethylamine in 90 to 80% hexanes) to afford 66 mg of 5-[4-methyl-4-(pyrrolidin-1-ylmethyl)-4,5-dihydro-1,3-oxazol-2-yl]-2-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridine 33.

Workup

  1. stirringthe solution is stirred for an additional 2 hours at room temperature
  2. stirringthe mixture stirred vigorously for 5 minutes
  3. extractionExtraction
  4. extractionorganic extract
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. concentrationconcentrated
  7. customto yield a brown oil
  8. customThe product is purified by chromatography over silicagel (eluent: gradient 10 to 20% triethylamine in 90 to 80% hexanes)

Sources & evidence

ORD record
ord-b4ce76a62b194b83976785491bf9fe14
Source dataset
uspto-grants-2011_01
Patent number
US07863450B2

Reaction notes

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