Water → N-tert-Butyl-2,6-di(pyrrolidin-1-yl)pyrimidin-4-amine

HRID 482324Notes

Reaction equation

HRID 482324 reaction equation
[C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.Cl[C:12]1[CH:17]=[C:16]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[N:15]=[C:14]([N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:13]=1.O>O1CCCC1.CCCCCC>[C:1]([NH:5][C:12]1[CH:17]=[C:16]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[N:15]=[C:14]([N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:13]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6385Tert-ButylamineHCID 7036994-Chloro-2,6-di(pyrrolidin-1-yl)pyrimidineHCID 178418339Butyllithium

Product 1

HCID 15338445N-tert-Butyl-2,6-di(pyrrolidin-1-yl)pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A mixture of 21.7 g of t-butylamine in 100 mL of tetrahydrofuran is cooled to about -40° and treated over about 15 min with 170 mL of 1.6M n-butyllithium in hexane. The mixture is warmed to 0° for 2 hr, then recooled to -40° and treated over 30 min with a mixture of 25 g of 4-chloro-2, 6-di-1-pyrrolidinylpyrimidine and 50 mL of tetrahydrofuran. The mixture is allowed to warm to 20°-25° and is stirred for 16-18 hr. Water (50 mL) is then added and the mixture is concentrated under reduced pressure. The residue is partitioned between methylene chloride and aqueous 10% sodium bicarbonate. The organic phase is washed with saline, dried over anhydrous sodium sulfate and concentrated. Chromatography (silica gel, 5% ethyl acetate/hexane) gives the title compound, NMR (CDCl3) 4.78, 4.25, 3.53-3.49, 3.40, 1.93-1.86 and 1.41 6.

Workup

  1. temperatureis cooled to about -40°
  2. temperatureThe mixture is warmed to 0° for 2 hr
  3. customrecooled to -40°
  4. temperatureto warm to 20°-25°
  5. concentrationthe mixture is concentrated under reduced pressure
  6. customThe residue is partitioned between methylene chloride and aqueous 10% sodium bicarbonate
  7. washThe organic phase is washed with saline
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2c92ee00222e477e863c28c47936c728
Source dataset
uspto-grants-1998_08
Patent number
US05795986

Reaction notes

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