Diisopropylethylamine → [2,2]Bipyrimidinyl-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide

HRID 2382032Notes

Reaction equation

HRID 2382032 reaction equation
[N:1]1[CH:6]=[C:5]([C:7]([OH:9])=O)[CH:4]=[N:3][C:2]=1[C:10]1[N:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[Cl-].[F:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([NH3+:27])[CH:22]=[C:21]2[CH3:28].CCN(C(C)C)C(C)C.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CN(C=O)C>[F:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([NH:27][C:7]([C:5]1[CH:4]=[N:3][C:2]([C:10]3[N:15]=[CH:14][CH:13]=[CH:12][N:11]=3)=[N:1][CH:6]=1)=[O:9])[CH:22]=[C:21]2[CH3:28]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 533964792-(Pyrimidin-2-yl)pyrimidine-5-carboxylic acidHCID 68554956HCID 68554956, compound

Product 1

HCID 59200005[2,2]Bipyrimidinyl-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amideYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of [2,2′]bipyrimidinyl-5-carboxylic acid (166 mg, 0.82 mmol), 5-fluoro-3-methyl-indol-1-yl-ammonium chloride (164 mg, 0.82 mmol) and DIPEA (106 mg, 0.82 mmol) in DMF (5 mL) is stirred at rt for 5 min. 4-(4,6-Dimethoxy-[1,3,5]triazin-2-yl)-4-methyl-morpholin-4-ium chloride (226 mg, 0.82 mmol) is added. The reaction mixture is heated to 50° C. for 1.5 h and then concentrated in vacuo. The residue is taken up in DMSO-d6 and then purified via reverse phase C18 HPLC chromatography eluting with water and acetonitrile containing 0.1% TFA buffer to afford [2,2]bipyrimidinyl-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide (56%). MS: 349 (M+H); 1H NMR (300 MHz, CDCl3): δ=2.27 (s, 3H), 7.05 (dt, 1H), 7.33 (s, 1H), 7.36 (dd, 1H), 7.42-7.46 (m, 1H), 7.72 (t, 1H), 9.07 (d, 2H), 9.51 (s, 2H), 12.17 (s, 1H).

Workup

  1. temperatureThe reaction mixture is heated to 50° C. for 1.5 h
  2. concentrationconcentrated in vacuo
  3. custompurified via reverse phase C18 HPLC chromatography
  4. washeluting with water and acetonitrile containing 0.1% TFA buffer

Sources & evidence

ORD record
ord-8539b3948d9748388535cab67fe76bb2
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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