1,1'-Carbonyldiimidazole → HCID 57508195, compound

HRID 14232Notes

Reaction equation

HRID 14232 reaction equation
Cl.[CH2:2]([N:5]([CH2:16][CH2:17][CH3:18])[C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([CH3:15])[N:14]=1)[C:9]([OH:11])=O)[CH2:3][CH3:4].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.Cl.[NH2:33][C@@H:34]([CH2:48][C:49]1[CH:54]=[C:53]([F:55])[CH:52]=[C:51]([F:56])[CH:50]=1)[C@H:35]([OH:47])[CH2:36][NH:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][CH3:46])[CH:40]=1>C1COCC1.C(N(CC)CC)C.ClCCl>[F:55][C:53]1[CH:54]=[C:49]([CH:50]=[C:51]([F:56])[CH:52]=1)[CH2:48][C@H:34]([NH:33][C:9](=[O:11])[C:8]1[CH:12]=[C:13]([CH3:15])[N:14]=[C:6]([N:5]([CH2:2][CH2:3][CH3:4])[CH2:16][CH2:17][CH3:18])[CH:7]=1)[C@H:35]([OH:47])[CH2:36][NH:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][CH3:46])[CH:40]=1

Participants

7

Reactant 3

HCID 682631,1'-Carbonyldiimidazole2×HCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride2×HCID 57487394HCID 57487394, compound

Product 1

HCID 57508195HCID 57508195, compoundYield 18.1%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent3×

Procedure

To 2-(dipropylamino)-6-methylisonicotinic acid hydrochloride (approx. 0.4 mmol) in THF (3 mL) was added triethylamine (0.17 mL), followed by dichloromethane (2 mL) and then CDI (0.071 g, 0.44 mmol). After stirring for 1 h, a mixture of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride (0.163 g, 0.400 mmol), triethylamine (0.11 mL), and dichloromethane (approx. 2 mL) was added to the CDI mixture. The mixture was allowed to stir overnight, after which an additional 0.12 mL of triethylamine and 0.045 g of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride was added. After stirring for several more hours, the mixture was partitioned between dichloromethane and aq. sodium bicarbonate. The organic layer was dried with sodium sulfate, concentrated, and the residue was chromatographed on silica gel using MeOH-dichloromethane (5/95) to give 0.04 g of the title compound.

Workup

  1. stirringto stir overnight
  2. stirringAfter stirring for several more hours
  3. customthe mixture was partitioned between dichloromethane and aq. sodium bicarbonate
  4. dry with materialThe organic layer was dried with sodium sulfate
  5. concentrationconcentrated
  6. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-d889d9e5be3f43d680c6403b2fbab73e
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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