Diisopropylethylamine → 2-tert-butyl-N-[(3S,5R)-5-(1-hydroxycyclohexyl)piperidin-3-yl]-4-[(3-methoxypropyl)amino]-N-(2-methylpropyl)pyrimidine-5-carboxamide dihydrochloride

HRID 2192843Notes

Reaction equation

HRID 2192843 reaction equation
[OH:1][C:2]1([C@@H:8]2[CH2:13][C@H:12]([NH:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(N(CC)C(C)C)(C)C.[C:35]([C:39]1[N:44]=[C:43]([NH:45][CH2:46][CH2:47][CH2:48][O:49][CH3:50])[C:42]([C:51]([Cl:53])=[O:52])=[CH:41][N:40]=1)([CH3:38])([CH3:37])[CH3:36]>ClCCCl>[ClH:53].[ClH:53].[C:35]([C:39]1[N:44]=[C:43]([NH:45][CH2:46][CH2:47][CH2:48][O:49][CH3:50])[C:42]([C:51]([N:14]([C@H:12]2[CH2:13][C@@H:8]([C:2]3([OH:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]3)[CH2:9][NH:10][CH2:11]2)[CH2:15][CH:16]([CH3:17])[CH3:18])=[O:52])=[CH:41][N:40]=1)([CH3:38])([CH3:36])[CH3:37]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 59625268tert-butyl (3R,5S)-3-(1-hydroxycyclohexyl)-5-[(2-methylpropyl)amino]piperidine-1-carboxylateHCID 866492962-Tert-butyl-4-[(3-methoxypropyl)amino]pyrimidine-5-carbonyl chloride

Product 1

HCID 684341782-tert-butyl-N-[(3S,5R)-5-(1-hydroxycyclohexyl)piperidin-3-yl]-4-[(3-methoxypropyl)amino]-N-(2-methylpropyl)pyrimidine-5-carboxamide dihydrochlorideYield 0.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

tert-Butyl (3R,5S)-3-(1-hydroxycyclohexyl)-5-[(2-methylpropyl)amino]piperidine-1-carboxylate (0.92 g) and N,N-diisopropylethylamine (1.0 g) were dissolved in 1,2-dichloroethane (10 ml), 2-tert-butyl-4-[(3-methoxypropyl)amino]pyrimidine-5-carbonyl chloride (0.74 g) was added under ice-cooling, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated, and diluted with aqueous calcium carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in 4 N hydrogen chloride-ethyl acetate (1 ml), and the mixture was stirred at room temperature for 0.5 hr. The reaction mixture was concentrated and purified by HPLC. The concentrate was dissolved in 4 N hydrogen chloride-ethyl acetate (1 ml) and concentrated to give the object compound (5.9 mg).

Workup

  1. temperaturecooling
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with aqueous calcium carbonate solution
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. dissolutionThe residue was dissolved in 4 N hydrogen chloride-ethyl acetate (1 ml)
  9. stirringthe mixture was stirred at room temperature for 0.5 hr
  10. concentrationThe reaction mixture was concentrated
  11. custompurified by HPLC
  12. dissolutionThe concentrate was dissolved in 4 N hydrogen chloride-ethyl acetate (1 ml)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-f423b1427996493baec477a36c9f58f2
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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