Triethylamine → N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-(dipropylamino)-6-methylpyrimidine-4-carboxamide

HRID 349025Notes

Reaction equation

HRID 349025 reaction equation
[CH2:1]([N:4]([CH2:15][CH2:16][CH3:17])[C:5]1[N:10]=[C:9]([C:11]([OH:13])=O)[CH:8]=[C:7]([CH3:14])[N:6]=1)[CH2:2][CH3:3].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.Cl.[NH2:32][C@@H:33]([CH2:47][C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=1)[C@H:34]([OH:46])[CH2:35][NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][CH3:45])[CH:39]=1.C(N(CC)CC)C>C1COCC1.ClCCl>[F:54][C:52]1[CH:53]=[C:48]([CH:49]=[C:50]([F:55])[CH:51]=1)[CH2:47][C@H:33]([NH:32][C:11]([C:9]1[CH:8]=[C:7]([CH3:14])[N:6]=[C:5]([N:4]([CH2:1][CH2:2][CH3:3])[CH2:15][CH2:16][CH3:17])[N:10]=1)=[O:13])[C@H:34]([OH:46])[CH2:35][NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][CH3:45])[CH:39]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-Carbonyldiimidazole2×HCID 210854602-(Dipropylamino)-6-methylpyrimidine-4-carboxylic acidHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

Product 1

HCID 58802606N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-(dipropylamino)-6-methylpyrimidine-4-carboxamideYield 84.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 2-(dipropylamino)-6-methylpyrimidine-4-carboxylic acid (0.101 g, 0.426 mmol) in THF (0.5 mL) was added 1,1′-carbonyldiimidazole (CDI) (0.076 g, 0.468 mmol). After 50 min the CDI mixture was added to a mixture of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride (0.173 g, 0.425 mmol) and triethylamine (0.18 mL, 1.28 mmol) in THF (6 mL) and dichloromethane (2 mL). After stirring overnight, the solvents were removed under reduced pressure and the residue was partitioned between dichloromethane, aq. sodium bicarbonate, and aq. sodium bicarbonate-brine mixture. The organic layer was dried over sodium sulfate, concentrated, and the residue was chromatographed on silica gel using MeOH-dichloromethane (5/95) to give 0.199 g of the title compound as a solid.

Workup

  1. customthe solvents were removed under reduced pressure
  2. customthe residue was partitioned between dichloromethane, aq. sodium bicarbonate, and aq. sodium bicarbonate-brine mixture
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-0cd185f78e1b4ebb833a64cbd13a4bd0
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

Loading…