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

HRID 14235Notes

Reaction equation

HRID 14235 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-8fab5d3c58b0451aa8228a28c9c4a24f
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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