Diisopropylethylamine → 2-tert-butyl-4-[(3-methoxypropyl)amino]-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-6-oxo-1,6-dihydropyrimidine-5-carboxamide

HRID 2192842Notes

Reaction equation

HRID 2192842 reaction equation
[C:1]([C:5]1[NH:6][C:7](=[O:20])[C:8]([C:17]([OH:19])=O)=[C:9]([NH:11][CH2:12][CH2:13][CH2:14][O:15][CH3:16])[N:10]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:21][CH:22]([CH3:46])[CH2:23][NH:24][C@H:25]1[CH2:30][C@@H:29]([C:31]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[O:32])[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.ClC(N(C)C)=[N+](C)C>ClCCCl>[C:1]([C:5]1[NH:6][C:7](=[O:20])[C:8]([C:17]([N:24]([CH2:23][CH:22]([CH3:46])[CH3:21])[C@H:25]2[CH2:30][C@@H:29]([C:31]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)=[O:32])[CH2:28][NH:27][CH2:26]2)=[O:19])=[C:9]([NH:11][CH2:12][CH2:13][CH2:14][O:15][CH3:16])[N:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10989639Chloro-N,N,N',N'-tetramethylformamidinium HexafluorophosphateHCID 59356577tert-Butyl (3S,5R)-3-(isobutylamino)-5-(morpholine-4-carbonyl)piperidine-1-carboxylateHCID 1361605272-Tert-butyl-4-[(3-methoxypropyl)amino]-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid

Product 1

HCID 1361605252-tert-butyl-4-[(3-methoxypropyl)amino]-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-6-oxo-1,6-dihydropyrimidine-5-carboxamideYield 4.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

2-tert-Butyl-4-[(3-methoxypropyl)amino]-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid (280 mg), tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (250 mg) and N,N-diisopropylethylamine (640 mg) were dissolved in 1,2-dichloroethane (10 ml), chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (420 mg) was added 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 TFA (1 ml), and the mixture was stirred at room temperature for 0.5 hr. The reaction mixture was concentrated and purified by HPLC to give the object compound (15.8 mg).

Workup

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

Sources & evidence

ORD record
ord-2cfe2497625f4d1eb09e599e982954de
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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