Diisopropylethylamine → HCID 86687339, compound

HRID 573463Notes

Reaction equation

HRID 573463 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH:9]([CH:21]1[CH:28]2[CH2:29][CH:24]3[CH2:25][C:26]([OH:31])([CH2:30][CH:22]1[CH2:23]3)[CH2:27]2)[C:10]([N:12]1[CH2:17][CH:16]2[CH:14]([CH2:15]2)[CH:13]1[C:18]([NH2:20])=[O:19])=[O:11].[C:32]([O:36][C:37]([NH:39][CH:40]([CH:51]([CH3:53])[CH3:52])[C:41]([N:43]1[CH2:47][CH2:46][CH2:45][CH:44]1[C:48](O)=[O:49])=[O:42])=[O:38])([CH3:35])([CH3:34])[CH3:33].CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl>C1COCC1>[C:32]([O:36][C:37](=[O:38])[NH:39][CH:40]([C:41]([N:43]1[CH2:47][CH2:46][CH2:45][CH:44]1[C:48](=[O:49])[NH:8][CH:9]([CH:21]1[CH:22]2[CH2:23][CH:24]3[CH2:25][C:26]([OH:31])([CH2:27][CH:28]1[CH2:29]3)[CH2:30]2)[C:10]([N:12]1[CH2:17][CH:16]2[CH:14]([CH2:15]2)[CH:13]1[C:18](=[O:19])[NH2:20])=[O:11])=[O:42])[CH:51]([CH3:53])[CH3:52])([CH3:33])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 381418HCID 381418, compound2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67451046HCID 67451046, compound

Product 1

HCID 86687339HCID 86687339, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the stirred solution 1.7 gm (0.00380 moles) of 3-[2-Amino-2-(5-hydroxy-adamantan-2-yl)-acetyl]-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid amide trifluoro acetic acid of formula 35 and 1.19 gm (0.00380 moles) of 1-(2-tert-Butoxycarbonylamino-3-methyl-butyryl)-pyrrolidine-2-carboxylic acid (Formula 26) in THF was added into HoBT (0.6 gm) and DIPEA (1.3 ml) at room temperature and stirred for 10 minutes. To this stirred solution EDC.HCl (0.94 gm) and DIPEA (1.10 ml) were added at 0° C. and the reaction mixture was stirred over night at room temperature. THF was evaporated and residue was taken into EtOAC. The EtOAC layer was washed with 1N HCl and aq. NaHCO3 solution, dried and concentrated in vacuum to get crude product. The crude product was purified by silica gel column chromatography to get pure (1-{2-[2-(2-Carbamoyl-3-aza-bicyclo[3.1.0]hex-3-yl)-1-(5-hydroxy-adamantan-2-yl)-2-oxo-ethylcarbamoyl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid tert-butyl ester (Formula 36). (Yield: 1.7 gm)

Workup

  1. stirringthe reaction mixture was stirred over night at room temperature
  2. customTHF was evaporated
  3. washThe EtOAC layer was washed with 1N HCl and aq. NaHCO3 solution
  4. customdried
  5. concentrationconcentrated in vacuum
  6. customto get crude product
  7. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3bde273d3969421e9ae991aa548a8617
Source dataset
uspto-grants-2015_05
Patent number
US09029567B2

Reaction notes

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