L-Tartaric acid → HCID 67301025, compound

HRID 1192726Notes

Reaction equation

HRID 1192726 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[N:7]2.[C:22]([OH:31])(=[O:30])[C@@H:23]([C@H:25]([C:27]([OH:29])=[O:28])[OH:26])[OH:24]>C(O)C>[OH:26][C@H:25]([C@@H:23]([OH:24])[C:22]([OH:31])=[O:30])[C:27]([OH:29])=[O:28].[Cl:1][C:2]1[CH:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[N:7]2

Participants

4

Reactant 2

HCID 444305L-Tartaric acidHCID 58368464HCID 58368464, compound

Product 1

HCID 67301025HCID 67301025, compoundYield 73.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of (1S)-1-[5-chloro-8-(3-fluorophenyl)cinnolin-7-yl]ethanamine (43 g, 140 mmol, 80-90% ee) in ethanol (640 mL) at 60° C. was treated with a solution of L-tartaric acid (20 g, 130 mmol) in ethanol (430 mL). The flask containing the acid was rinsed with ethanol (12 ml) and the rinse solution was added to the reaction mixture at 60° C. The reaction mixture was stirred at 60° C. for 15 minutes and at room temperature for 18 hours. The solid that precipitated was collected by filtration and rinsed with ice-cold ethanol (9 mL) followed by 2-methoxy-2-methylpropane (3×18 ml) to give the desired product (43 g, 73%) as an off-white solid with 99.4% ee. 1H NMR determined that the amine to acid ratio was 1:0.75. LCMS for the free amine C16H14ClFN3 (M+H)+: m/z=302.1; Found: 302.0; 1H NMR (400 MHz, DMSO-d6): δ 9.53 (d, J=6.0 Hz, 1H), 8.47 (d, J=0.6 Hz, 1H), 8.35 (d, J=6.0 Hz, 1H), 7.62-7.54 (m, 1H), 7.37-7.19 (m, 3H), 4.18-4.13 (m, 1H), 3.92 (s, 1.5H, tartaric acid), 1.38-1.34 (m, 3H).

Workup

  1. additionThe flask containing the acid
  2. washwas rinsed with ethanol (12 ml)
  3. additionthe rinse solution was added to the reaction mixture at 60° C
  4. customThe solid that precipitated
  5. filtrationwas collected by filtration
  6. washrinsed with ice-cold ethanol (9 mL)

Sources & evidence

ORD record
ord-0321ba51719f4e0a821f9d0c9f601ec3
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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