N-methyl-2-pyrrolidone → 5-{9-Isobutyl-8-[4-(methylsulfonyl)-1,4-diazepan-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

HRID 421355

Reaction equation

HRID 421355 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CN1CCCC1=O.Cl[C:16]1[N:17]([CH2:38][CH:39]([CH3:41])[CH3:40])[C:18]2[C:23]([N:24]=1)=[C:22]([N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[N:21]=[C:20]([C:31]1[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=1)[N:19]=2.[S:42](Cl)([CH3:45])(=[O:44])=[O:43]>C(N(CC)CC)C>[CH2:38]([N:17]1[C:16]([N:1]2[CH2:7][CH2:6][CH2:5][N:4]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:3][CH2:2]2)=[N:24][C:23]2[C:18]1=[N:19][C:20]([C:31]1[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=1)=[N:21][C:22]=2[N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[CH:39]([CH3:41])[CH3:40]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 31297Methanesulfonyl chlorideHCID 68163Hexahydro-1,4-diazepineHCID 593335495-(8-Chloro-9-isobutyl-6-morpholino-9H-purin-2-yl)pyrimidin-2-amine

Product 1

HCID 593336605-{9-Isobutyl-8-[4-(methylsulfonyl)-1,4-diazepan-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amineYield 110.9%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
120 °C

Procedure

Homopiperazine (130 mg, 1.3 mmol) and N-methylpyrrolidone (1 ml) were added to 5-(8-chloro-9-isobutyl-6-morpholin-4-yl-9H-purin-2-yl)pyrimidin-2-amine (100 mg, 0.26 mmol) and the resulting mixture stirred at 120° C. for 2 hours. The reaction mixture was cooled and partitioned with methylene chloride and water, the organic layer was dried over magnesium sulfate, and the solvent was concentrated under reduced pressure. Triethylamine (110 μl) and mesyl chloride (45 μl, 0.58 mmol) were added to the resulting mixture and the resulting mixture was stirred for 0.5 hours. The reaction mixture was partitioned with ethyl acetate and water and the organic layer was dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by preparative HPLC (column, NOMURA Develosil Combi-RP-5; mobile phase, acetonitrile/water/formic acid) to give the title compound (153 mg, 75%) as a white solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned with methylene chloride and water
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. concentrationthe solvent was concentrated under reduced pressure
  5. stirringthe resulting mixture was stirred for 0.5 hours
  6. customThe reaction mixture was partitioned with ethyl acetate and water
  7. dry with materialthe organic layer was dried over magnesium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by preparative HPLC (column, NOMURA Develosil Combi-RP-5; mobile phase, acetonitrile/water/formic acid)

Sources & evidence

ORD record
ord-42295b25c6bb4432a476fc87dcd0cd31
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Linked notes

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