Diisopropylethylamine → HCID 46187142, compound

HRID 2081140Notes

Reaction equation

HRID 2081140 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][N:7]([C:13]([O:15][C@@H:16]1[CH2:20][C@@H:19]([C:21](=[O:37])[NH:22][C@:23]3([C:28](=[O:36])[NH:29][S:30]([CH:33]4[CH2:35][CH2:34]4)(=[O:32])=[O:31])[CH2:25][C@H:24]3[CH2:26][CH3:27])[NH:18][CH2:17]1)=[O:14])[CH2:8]2.[F:38][C:39]1[CH:40]=[C:41]([NH:49][C@@H:50]([C:54]([CH3:57])([CH3:56])[CH3:55])[C:51](O)=[O:52])[CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=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.OS([O-])(=O)=O.[K+]>C(Cl)Cl.O>[Cl:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][N:7]([C:13]([O:15][C@@H:16]1[CH2:20][C@@H:19]([C:21](=[O:37])[NH:22][C@:23]3([C:28](=[O:36])[NH:29][S:30]([CH:33]4[CH2:34][CH2:35]4)(=[O:32])=[O:31])[CH2:25][C@H:24]3[CH2:26][CH3:27])[N:18]([C:51](=[O:52])[C@@H:50]([NH:49][C:41]3[CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=[C:39]([F:38])[CH:40]=3)[C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:17]1)=[O:14])[CH2:8]2

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516920Potassium bisulfateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57988400HCID 57988400, compoundHCID 67103382HCID 67103382, compound

Product 1

HCID 46187142HCID 46187142, compoundYield 65.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

(3R,5S)-5-((1R,2R)-1-(cyclopropylsulfonylcarbamoyl)-2-ethylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-chloroisoindoline-2-carboxylate dihydrochloride (0.040 g, 0.071 mmol), (S)-2-(3-fluoro-5-(trifluoromethyl)phenylamino)-3,3-dimethylbutanoic acid (0.023 g, 0.079 mmol) and HATU (0.042 g, 0.11 mmol) in DCM (3 mL) was added DIEA (0.048 mL, 0.28 mmol) and the reaction was stirred at rt for 5 hr. H2O (5 mL) and saturated KHSO4 solution (3 mL) was added. The mixture was extracted with ether (15 mL), washed with brine (10 mL) and dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (hexane:Ethyl acetate=1:2) to give the (3R,5S)-5-((1R,2R)-1-(cyclopropylsulfonylcarbamoyl)-2-ethylcyclopropylcarbamoyl)-1-((S)-2-(3-fluoro-5-(trifluoromethyl)phenylamino)-3,3-dimethylbutanoyl)pyrrolidin-3-yl 4-chloroisoindoline-2-carboxylate (0.037 g, 65%) as white solid. MS: Calcd.: 799.2; Found: [M+H]+ 800.1. 1H NMR (400 MHz, d6-DMSO). 10.44 (s, 1H), 8.80 & 8.74 (s, 1H), 7.34 (m, 3H), 7.14 & 7.02 (m, 1H), 6.73 (m, 1H), 6.35 & 6.26 (d, J=8.4 Hz, 1H), 6.15 (m, 1H), 5.35 (m, 1H), 4.50-4.72 (m, 3H), 4.20-4.46 (m, 4H), 3.82 (m, 1H), 2.94 (m, 1H), 2.31 (m, 1H), 2.04 (m, 1H), 0.84-1.49 (m, 21H).

Workup

  1. extractionThe mixture was extracted with ether (15 mL)
  2. washwashed with brine (10 mL)
  3. dry with materialdried over sodium sulfate
  4. customAfter removal of solvent
  5. customthe residue was purified by chromatography (hexane:Ethyl acetate=1:2)

Sources & evidence

ORD record
ord-cefb2453664940039a037829f009dbbb
Source dataset
uspto-grants-2011_04
Patent number
US07932277B2

Reaction notes

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