4-Methylmorpholine → tert-butyl (2S)-1-((1S,3aR,6aS)-1-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)hexahydrocyclopenta-[c]pyrrol-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

HRID 424973Notes

Reaction equation

HRID 424973 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:10]([N:12]1[CH2:16][C@@H:15]2[CH2:17][CH2:18][CH2:19][C@@H:14]2[C@H:13]1[C:20](O)=[O:21])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:55][C@@H:56]([CH2:65][CH2:66][CH3:67])[CH:57]([OH:64])[C:58]([NH:60][CH:61]1[CH2:63][CH2:62]1)=[O:59].Cl.N[C@@H](CCC)C(O)C(NC1CC1)=O>ClCCl.CN(C)C=O.O>[CH:61]1([NH:60][C:58](=[O:59])[CH:57]([OH:64])[C@@H:56]([NH:55][C:20]([C@@H:13]2[C@H:14]3[CH2:19][CH2:18][CH2:17][C@H:15]3[CH2:16][N:12]2[C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:65][CH2:66][CH3:67])[CH2:63][CH2:62]1

Participants

10

Reactant 6

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 23634853(3S)-3-Amino-N-cyclopropyl-2-hydroxyhexanamideHCID 59677749(1S,3aR,6aS)-2-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acidHCID 66656935Hexanamide, 3-amino-N-cyclopropyl-2-hydroxy-, hydrochloride (1:1), (3S)-

Product 1

HCID 57930532tert-butyl (2S)-1-((1S,3aR,6aS)-1-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)hexahydrocyclopenta-[c]pyrrol-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

The crude (1S,3aR,6aS)-2-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid from Example 10 was dissolved in dichloromethane (4 mL) and treated with 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (EDCI) (71 mg, 2 eq), 1-hydroxybenzotriazole (HOBT) (57 mg, 2 eq) and N-methyl morpholine (0.2 mL, 5 eq) at room temperature. To this mixture was added after 30 minutes (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide, the compound of formula (12) (1 eq) in dichloromethane (3 mL) and N,N-dimethylformamide (3 mL) and the reaction mixture was stirred at room temperature. After 18 hours the reaction mixture was diluted with water, and the product extracted into ethyl acetate. The organic extract was washed with brine, dried and evaporated to dryness under reduced pressure, to give crude tert-butyl (2S)-1-((1S,3aR,6aS)-1-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)hexahydrocyclopenta-[c]pyrrol-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate, the compound of formula (17).

Workup

  1. extractionthe product extracted into ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with brine
  4. customdried
  5. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-9396a053a37e483d8d6635c38edf50fa
Source dataset
uspto-grants-2012_01
Patent number
US08106059B2

Reaction notes

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