Diisopropylethylamine → HCID 86723607, compound

HRID 590672Notes

Reaction equation

HRID 590672 reaction equation
[N:1]1([C:19]([O:21]C(C)(C)C)=O)[C@H:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH2:4][C@@H:3]2[CH2:16][CH2:17][CH2:18][C@H:2]12.[CH3:26][O:27][C:28]([NH:30][C@@H:31]([C@@H:35]([CH3:38])[CH2:36][CH3:37])C(O)=O)=[O:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:26][O:27][C:28]([NH:30][C@@H:31]([C@@H:35]([CH3:38])[CH2:36][CH3:37])[C:19]([N:1]1[C@H:5]([C:6]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:7])[CH2:4][C@@H:3]2[CH2:16][CH2:17][CH2:18][C@H:2]12)=[O:21])=[O:29]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14514526HCID 14514526, compoundHCID 28378062L-Isoleucine, N-(methoxycarbonyl)-

Product 1

HCID 86723607HCID 86723607, compoundYield 132.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of commercially available (2S,3aS,6aS)-2-benzyl 1-tert-butyl hexahydrocyclopenta[b]pyrrole-1,2(2H)-dicarboxylate (10.0 g, 35.489 mmol) in methylene chloride (100 mL) was added (2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoic acid (10.072 g, 53.23 mmol), HATU (21.59 g, 56.78 mmol), and DIPEA (18.59 mL, 106.46 mmol). The reaction was stirred overnight, at which time it was concentrated in vacuo, diluted in ethyl acetate and washed with HCl (1N). The aqueous layer was backextracted with ethyl acetate, and the combined organics were dried over sodium sulphate, filtered and concentrated. The resulting oil was diluted in a small amount of chloroform and filtered to remove tetramethyl urea precipitate. The resulting oil was purified by normal phase chromatography (50% ethyl acetate in hexanes) to give (2S,3aS,6aS)-benzyl 1-((2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoyl)octahydrocyclopenta[b]pyrrole-2-carboxylate (19.53 g, >99% yield) which was used without further purification. LCMS-ESI+ calc'd for C23H33N2O5: 417.23. Found: 417.37.

Workup

  1. concentrationwas concentrated in vacuo
  2. additiondiluted in ethyl acetate
  3. washwashed with HCl (1N)
  4. dry with materialthe combined organics were dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionThe resulting oil was diluted in a small amount of chloroform
  8. filtrationfiltered
  9. customto remove tetramethyl urea precipitate
  10. customThe resulting oil was purified by normal phase chromatography (50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8b65bb53fbe0496598829f756dd6e35d
Source dataset
uspto-grants-2016_01
Patent number
US09233974B2

Reaction notes

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