Diisopropylethylamine → HCID 57988410, compound

HRID 2081127Notes

Reaction equation

HRID 2081127 reaction equation
Cl.[CH:2]1([S:5]([NH:8][C:9]([C@@:11]2([NH:16][C:17]([C@H:19]3[NH:23][CH2:22][C@H:21]([O:24][C:25]([N:27]4[CH2:35][C:34]5[C:29](=[CH:30][CH:31]=[CH:32][C:33]=5[F:36])[CH2:28]4)=[O:26])[CH2:20]3)=[O:18])[CH2:13][C@H:12]2[CH:14]=[CH2:15])=[O:10])(=[O:7])=[O:6])[CH2:4][CH2:3]1.[F:37][C:38]1[CH:43]=[CH:42][C:41]([NH:44][C@@H:45]([CH:49]([CH3:51])[CH3:50])[C:46](O)=[O:47])=[CH:40][CH:39]=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>[F:36][C:33]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:34]=1[CH2:35][N:27]([C:25]([O:24][C@@H:21]1[CH2:20][C@@H:19]([C:17](=[O:18])[NH:16][C@:11]3([C:9](=[O:10])[NH:8][S:5]([CH:2]4[CH2:3][CH2:4]4)(=[O:6])=[O:7])[CH2:13][C@H:12]3[CH:14]=[CH2:15])[N:23]([C:46](=[O:47])[C@@H:45]([NH:44][C:41]3[CH:40]=[CH:39][C:38]([F:37])=[CH:43][CH:42]=3)[CH:49]([CH3:51])[CH3:50])[CH2:22]1)=[O:26])[CH2:28]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 51776821HCID 51776821, compoundHCID 86636567HCID 86636567, compound

Product 1

HCID 57988410HCID 57988410, compoundYield 65.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

[(3R,5S)-5-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl]4-fluoroisoindoline-2-carboxylate hydrochloride (0.050 g, 0.092 mmol), (S)-2-(4-fluorophenylamino)-3-methylbutanoic acid (0.021 g, 0.10 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,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-1-((S)-2-(4-fluorophenylamino)-3-methylbutanoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate (0.042 g, 65%) as white solid. MS: Calcd.: 699; Found: [M+H]+ 700. 1H NMR (400 MHz, d6-DMSO) δ 10.91, 10.85 & 10.58 (s, 1H), 9.16, 9.05 & 8.84 (s, 1H), 7.40 (m, 1H), 7.04-7.21 (m, 2H), 6.71 (m, 2H), 6.60 (m, 2H), 5.62 (m, 1H), 5.10-5.17 (m, 4H), 4.68 (s, 2H), 4.41-4.60 (m, 2H), 4.32 (m, 1H), 4.09 (m, 1H), 3.97 (m, 1H), 3.80 (m, 1H), 2.94 (m, 1H), 2.22 (m 1H), 2.00-2.18 (m, 3H), 1.71 (m, 1H), 1.20-1.31 (m, 2H), 0.87-1.10 (m, 9H).

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-6ae411a5fc0344b7a1a52423d6f07ba5
Source dataset
uspto-grants-2011_04
Patent number
US07932277B2

Reaction notes

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