Trimethyl orthoformate → HCID 178428190, compound

HRID 2175056Notes

Reaction equation

HRID 2175056 reaction equation
Cl.Cl.[F:3][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH:10]2[NH:13][C:14]2[C:19]([NH2:20])=[CH:18][CH:17]=[C:16]([NH:21][C:22]3[NH:23][N:24]=[C:25]([CH3:27])[CH:26]=3)[N:15]=2)=[CH:6][CH:5]=1.[CH:28](OC)(OC)OC>C(O)(=O)C>[F:3][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][C@H:10]2[N:13]2[C:14]3=[N:15][C:16]([NH:21][C:22]4[NH:23][N:24]=[C:25]([CH3:27])[CH:26]=4)=[CH:17][CH:18]=[C:19]3[N:20]=[CH:28]2)=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 9005Trimethyl orthoformateHCID 178428234HCID 178428234, compound

Product 1

HCID 178428190HCID 178428190, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Dissolve N2-(6-fluoroindan-1-yl)-N6-(5-methyl-2H-pyrazol-3-yl)-pyridine-2,3,6-triamine dihydrochloride in acetic acid (5 mL) and trimethyl orthoformate (0.68 mL, 6.20 mmol). Stir under nitrogen for 30 minutes. Concentrate in vacuo and purify by reverse phase chromatography, eluting with a gradient of 0.03% aqueous hydrochloric acid in acetonitrile to give the racemate of the title compound (0.124 g, 19%, 2 steps). MS (ES) m/z=349 [M+1]. Separate the racemate with chiral chromatography conditions to give the title compound: (70 mg, 11%. Enantiomer 1 (first eluent at 3.7 min)>99% ee, 100% MeOH, 0.2% DMEA, 1.0 mL/min, 4.6×150 mm, CHIRALPAK® AD-H).

Workup

  1. concentrationConcentrate in vacuo
  2. custompurify by reverse phase chromatography
  3. washeluting with a gradient of 0.03% aqueous hydrochloric acid in acetonitrile

Sources & evidence

ORD record
ord-5e6bf1ce52654ee58da0f1702d79e5be
Source dataset
uspto-grants-2015_06
Patent number
US09062050B2

Reaction notes

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