Ethyl Acetate → HCID 67959575, compound

HRID 1427796Notes

Reaction equation

HRID 1427796 reaction equation
ClC(Cl)(Cl)CO[C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:45])[C@@H:14]([NH:30][C:31](=[O:44])[C@@H:32]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH:33]([CH3:35])[CH3:34])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH:17]=2)[NH:8]1)=[O:6].C(=O)(O)[O-].[Na+].[I:53][C:54]1[CH:55]=[C:56]([CH:59]=[CH:60][CH:61]=1)[CH2:57][NH2:58].C(OCC)(=O)C>O1CCCC1>[C:40]([O:39][C:37](=[O:38])[NH:36][C@H:32]([C:31](=[O:44])[NH:30][C@@H:14]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][Si:23]([C:26]([CH3:28])([CH3:27])[CH3:29])([CH3:25])[CH3:24])[CH:17]=1)[C:13]([N:9]1[CH2:10][CH2:11][CH2:12][C@@H:7]([C:5](=[O:6])[NH:58][CH2:57][C:56]2[CH:59]=[CH:60][CH:61]=[C:54]([I:53])[CH:55]=2)[NH:8]1)=[O:45])[CH:33]([CH3:34])[CH3:35])([CH3:41])([CH3:43])[CH3:42]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 970123-IodobenzylamineHCID 516892Sodium BicarbonateHCID 71225144HCID 71225144, compound

Product 1

HCID 67959575HCID 67959575, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-1-{(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (987 mg, 1.337 mmol) in tetrahydrofuran (20 mL) was treated with sodium bicarbonate (337 mg, 4.011 mmol) and 3-Iodo-benzylamine (467 mg, 2.005 mmol). After overnight stirring, ethyl acetate and silica were added and the volatiles removed in vacuo. The product was purified by silica gel chromatography using iso-hexanes/ethyl acetate, 1:0 then 1:2 to afford the title compound (374 mg, 34%) as a white solid. 1H NMR (300 MHz, CDCl3) δ0.17 (s, 3H), 0.18 (s 3H), 0.81 (d, J=6.9 Hz, 3H), 0.86 (d, J=7.1 Hz, 3H), 0.97 (s, 9H), 1.46 (s, 9H), 1.61-1.70 (m, 2H), 1.73-1.83 (m, 1H), 1.84-1.94 (m, 1H), 1.96-2.05 (m, 1H), 2.53-2.66 (m, 1H), 2.81-3.01 (m, 3H), 3.34-3.45 (m, 1H), 3.74 (t, J=6.0 Hz, 1H), 3.98-4.09 (m, 1H), 4.31-4.51 (m, 2H), 4.79-4.88 (m, 1H), 5.75 (q, J=8.7 Hz, 1H), 6.38-6.49 (m, 1H), 6.67-6.73 (m, 1H), 6.74-6.78 (m, 1H), 6.84 (d, J=7.6 Hz, 1H), 7.03-7.15 (m, 2H), 7.31 (s, 1H), 7.33-7.43 (m, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.67 (s, 1H).

Workup

  1. customthe volatiles removed in vacuo
  2. customThe product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-94a3eb5dcbc148e3ab6479d44e8b476a
Source dataset
uspto-grants-2015_01
Patent number
US08933015B2

Reaction notes

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