Diisopropylethylamine → HCID 86706126, compound

HRID 2176280Notes

Reaction equation

HRID 2176280 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15](/[CH:21]=[CH:22]/[C@:23]([CH2:28][O:29][CH3:30])([CH3:27])[C:24]([OH:26])=[O:25])=[CH:16][CH:17]=2)[N:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:31][C:32]([Cl:56])([Cl:55])[CH2:33][O:34][C:35]([C@@H:37]1[CH2:42][CH2:41][CH2:40][N:39]([C:43](=[O:54])[C@@H:44]([NH:46][C:47](=[O:53])[C@@H:48](O)[CH:49]([CH3:51])[CH3:50])[CH3:45])[NH:38]1)=[O:36].C(N(CC)C(C)C)(C)C.CC1C=CC=C([N+]([O-])=O)C=1C(OC(=O)C1C([N+]([O-])=O)=CC=CC=1C)=O.C(=O)([O-])O.[Na+]>ClCCl.CN(C)C1C=CN=CC=1>[Cl:55][C:32]([Cl:31])([Cl:56])[CH2:33][O:34][C:35]([C@@H:37]1[CH2:42][CH2:41][CH2:40][N:39]([C:43](=[O:54])[C@@H:44]([NH:46][C:47](=[O:53])[C@@H:48]([O:25][C:24](=[O:26])[C@@:23]([CH2:28][O:29][CH3:30])([CH3:27])/[CH:22]=[CH:21]/[C:15]2[CH:14]=[C:13]3[C:18]([CH:19]=[CH:20][C:11]([C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH3:10])=[N:12]3)=[CH:17][CH:16]=2)[CH:49]([CH3:50])[CH3:51])[CH3:45])[NH:38]1)=[O:36]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 104726482-Methyl-6-nitrobenzoic anhydrideHCID 86706052HCID 86706052, compoundHCID 86706125HCID 86706125, compound

Product 1

HCID 86706126HCID 86706126, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (E)-(S)-4-[2-((R)-1-tert-butoxycarbonylamino-ethyl)-quinolin-7-yl]-2-methoxymethyl-2-methyl-but-3-enoic acid (176 mg, 0.34 mmol) in dichloromethane (2 mL), was added (S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (205 mg, 0.47 mmol), 4-dimethylaminopyridine (116 mg, 0.95 mmol), N,N-diisopropylethylamine (123 mg, 0.95 mmol) and 2-methyl-6-nitrobenzoic anhydride (164 mg, 0.47 mmol). The reaction mixture was stirred at room temperature for 18 h, was then treated with saturated solution of sodium hydrogen carbonate, extracted with dichloromethane (2×) and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated. The crude residue was purified by silica gel chromatography using a Biotage KP-Sil 50 g cartridge eluting with a gradient of iso-hexanes/ethyl acetate 9:1 to 0:1 to give the title product (0.22 g, 78%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 0.85-1.10 (m, 6H), 1.20-1.70 (m, 23H), 2.05-2.20 (m, 1H), 2.30-2.45 (m, 1H), 3.44 (s, 3H), 3.60-3.95 (m, 4H), 4.15-4.32 (m, 1H), 4.68-4.70 (m, 1H), 4.90-5.05 (m, 2H), 5.20-5.45 (m, 1H), 6.10-6.28 (m, 1H), 6.60-6.85 (m, 2H), 7.10-7.20 (m, 1H), 7.28 (d, J=8.4 Hz, 1H), 7.66-7.74 (m, 2H), 8.00 (d, J=4.0 Hz, 1H), 8.05 (d, J=8.4 Hz, 1H). LCMS (m/z) 828.5 [M+H], Tr=3.48 min.

Workup

  1. extractionextracted with dichloromethane (2×)
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customThe filtrate was evaporated
  6. customThe crude residue was purified by silica gel chromatography
  7. washeluting with a gradient of iso-hexanes/ethyl acetate 9:1 to 0:1

Sources & evidence

ORD record
ord-d0d89f8e69ca4126b436c68ec87cde05
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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