Diisopropylethylamine → HCID 86636566, compound

HRID 2081126Notes

Reaction equation

HRID 2081126 reaction equation
C(OC([N:8]1[CH2:12][C@H:11]([O:13][C:14]([N:16]2[CH2:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][C:22]=3[Cl:25])[CH2:17]2)=[O:15])[CH2:10][C@H:9]1[C:26]([OH:28])=O)=O)(C)(C)C.Cl.[NH2:30][C@:31]1([C:37]([NH:39][S:40]([CH:43]2[CH2:45][CH2:44]2)(=[O:42])=[O:41])=[O:38])[CH2:33][C@H:32]1[CH:34]1[CH2:36][CH2:35]1.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>CN(C=O)C.O>[ClH:25].[CH:43]1([S:40]([NH:39][C:37]([C@@:31]2([NH:30][C:26]([C@H:9]3[NH:8][CH2:12][C@H:11]([O:13][C:14]([N:16]4[CH2:24][C:23]5[C:18](=[CH:19][CH:20]=[CH:21][C:22]=5[Cl:25])[CH2:17]4)=[O:15])[CH2:10]3)=[O:28])[CH2:33][C@H:32]2[CH:34]2[CH2:36][CH2:35]2)=[O:38])(=[O:42])=[O:41])[CH2:45][CH2:44]1

Participants

7

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 57437882HCID 57437882, compoundHCID 57463496HCID 57463496, compound

Product 1

HCID 86636566HCID 86636566, compoundYield 163.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(2S,4R)-1-(tert-butoxycarbonyl)-4-(4-chloroisoindoline-2-carbonyloxy)pyrrolidine-2-carboxylic acid 26 (0.35 g, 0.852 mmol), (1R,2S)-1-amino-2-cyclopropyl-N-(cyclopropylsulfonyl)cyclopropanecarboxamide hydrochloride 25 (0.287 g, 1.02 mmol) and HATU (0.389 g, 1.02 mmol) were dissolved in DriSolve DMF (8.5 mL), and cooled in an ice bath. DIEA (d 0.742) (0.445 ml, 2.56 mmol) was then added to reaction drop-wise. The reaction was allowed to warm up to rt slowly and stirred overnight. After reaching completion, the reaction was diluted with water (120 mL) and extracted with EtOAc (3×150 mL). The combined organic extract was washed with 0.5 N HCl (200 mL), brine (150 mL) and dried over Na2SO4. Removal of solvent yielded the crude product as a light yellowish foamy solid, which was purified by reverse phase chromatography (eluent: 5 to 95% MeCN/water), giving pure desired product as a white solid (0.40 g, 70% yield). LCMS (APCI+): 537.2 (MH+−Boc).

Workup

  1. temperaturecooled in an ice bath
  2. extractionextracted with EtOAc (3×150 mL)
  3. extractionThe combined organic extract
  4. washwas washed with 0.5 N HCl (200 mL), brine (150 mL)
  5. dry with materialdried over Na2SO4
  6. customRemoval of solvent
  7. customyielded the crude product as a light yellowish foamy solid, which
  8. customwas purified by reverse phase chromatography (eluent: 5 to 95% MeCN/water)

Sources & evidence

ORD record
ord-6cb1c2a6c9144d6692d476f0a5045379
Source dataset
uspto-grants-2011_04
Patent number
US07932277B2

Reaction notes

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