N,N,N',N'-Tetramethylethylenediamine → HCID 86667340, compound

HRID 334121Notes

Reaction equation

HRID 334121 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[N:3]=1.CN(C)CCN(C)C.C([Li])CCC.CCCCCC.[Br:42][CH2:43][CH2:44][CH2:45][CH2:46]Br>C1COCC1>[Br:42][CH2:43][CH2:44][CH2:45][CH2:46][C:7]1[N:8]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[C:9]2[C:5]([N:6]=1)=[C:4]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)[N:3]=[C:2]([Cl:1])[N:10]=2

Participants

7

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 80561,4-DibromobutaneHCID 8058HexaneHCID 134629464-(2-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholineHCID 178418339Butyllithium

Product 1

HCID 86667340HCID 86667340, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-(2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholine (Example 118) (5.0 g, 15 mmol) and N,N,N′,N′-tetramethylethylenediamine (3.5 mL, 23 mmol) in THF (110 mL) was cooled to −42° C. and treated with a solution of 2.5M n-Butyllithium in hexane (22 mL, 54 mmol) drop-wise over 5 minutes. After 30 minutes at −42° C., 1,4-dibromo-butane (8.9 mL, 75 mmol) was added and the reaction mixture was slowly warmed to 0° C. over 1 hr and then warmed to ambient temperature for 90 minutes. The mixture was quenched with a saturated solution of NH4Cl, and diluted with ethyl acetate. The aqueous layer was extracted into ethyl acetate (3×), and the combined organics were dried over sodium sulfate, filtered, and absorbed onto celite for purification by flash chromatography to afford 4-(8-(4-bromobutyl)-2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholine as a white solid (1.1 g, 15%). LC/MS (ESI+): m/z 459 (M+H)

Workup

  1. temperaturewarmed to ambient temperature for 90 minutes
  2. customThe mixture was quenched with a saturated solution of NH4Cl
  3. additiondiluted with ethyl acetate
  4. extractionThe aqueous layer was extracted into ethyl acetate (3×)
  5. dry with materialthe combined organics were dried over sodium sulfate
  6. filtrationfiltered
  7. customabsorbed onto celite for purification by flash chromatography

Sources & evidence

ORD record
ord-e469092b098642e1a201161b4eda3f58
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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