Ethanol → HCID 86695515, compound

HRID 1487557Notes

Reaction equation

HRID 1487557 reaction equation
[CH3:1][N:2]([CH3:4])[CH3:3].C(O)C.[Br:8][CH2:9][CH2:10][CH2:11][C:12]([O:14][C@H:15]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]=[N:33][C:34]([CH2:37][NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:36]=2)=[CH:27][CH:26]=1)[C@H:16]([NH:19][C:20](=[O:24])[CH:21]([F:23])[F:22])[CH2:17][F:18])=[O:13]>O1CCCC1>[Br-:8].[F:22][CH:21]([F:23])[C:20]([NH:19][C@H:16]([CH2:17][F:18])[C@H:15]([O:14][C:12](=[O:13])[CH2:11][CH2:10][CH2:9][N+:2]([CH3:4])([CH3:3])[CH3:1])[C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]=[N:33][C:34]([CH2:37][NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:36]=2)=[CH:27][CH:26]=1)=[O:24]

Participants

5

Reactant 3

HCID 702EthanolHCID 1146TrimethylamineHCID 86695513HCID 86695513, compound

Product 1

HCID 86695515HCID 86695515, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

In a sealed tube 4.2 M trimethylamine in ethanol (1.42 mL, 5.98 mmol) is added to a stirred solution of (1R,2S)-2-[(difluoroacetyl)amino]-3-fluoro-1-[4-(6-{[(methylsulfonyl)amino]methyl}pyridin-3-yl)phenyl]propyl 4-bromobutanoate (Step 1, 570.0 mg, 0.982 mmol) in tetrahydrofuran (11.0 mL) at room temperature and the reaction mixture was heated at 50° C. overnight. After stirring overnight the reaction mixture was concentrated and the residue was taken up in water. The aqueous layer was extracted with methylene chloride (3×) to remove all the impurities. The aqueous layer was then lyophilized overnight to afford the title compound (375 mg): 1H NMR (300 MHz, DMSO-d6) δ 1.94-1.97 (m, 2H), 2.73-2.77 (t, 2H), 3.05 (s, 9H), 3.23-3.31 (m, 2H), 3.48 (s, 3H), 4.27-4.33 (m, 1.5H), 4.43-4.53 (m, 1H), 4.67-4.71 (m, 0.5H), 4.89-4.91 (m, 1H), 5.13 (s, 2H), 5.91 (d, 1H), 6.20 (t, 1H), 7.45-7.48 (m, 3H), 7.71 (d, 2H), 8.10-8.14 (dd, 1H), 8.82 (d, 1H), 8.86 (d, 1H). MS (ESI+) m/z 559.1 [M].

Workup

  1. concentrationwas concentrated
  2. extractionThe aqueous layer was extracted with methylene chloride (3×)
  3. customto remove all the impurities
  4. waitThe aqueous layer was then lyophilized overnight

Sources & evidence

ORD record
ord-452b2ada756e43f7b6c9135779c1f34a
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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