Diisopropylethylamine → 2-Thiazol-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide

HRID 2382028Notes

Reaction equation

HRID 2382028 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[N:11]=[CH:10][C:9]([C:12]([OH:14])=O)=[CH:8][N:7]=1.[Cl-].[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([NH3+:26])[CH:21]=[C:20]2[CH3:27].C(N(C(C)C)CC)(C)C.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CN(C=O)C>[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([NH:26][C:12]([C:9]1[CH:10]=[N:11][C:6]([C:2]3[S:1][CH:5]=[CH:4][N:3]=3)=[N:7][CH:8]=1)=[O:14])[CH:21]=[C:20]2[CH3:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 68554956HCID 68554956, compoundHCID 685552372-(Thiazol-2-YL)pyrimidine-5-carboxylic acid

Product 1

HCID 592000152-Thiazol-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amideYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-thiazol-2-yl-pyrimidine-5-carboxylic acid (50 mg, 0.244 mmol), 5-fluoro-3-methyl-indol-1-yl-ammonium chloride (49 mg, 0.244 mmol), diisopropylethylamine (31.5 mg, 0.244 mmol) in DMF (1 mL) is stirred at rt for 5 min. 4-(4,6-Dimethoxy-[1,3,5]triazin-2-yl)-4-methyl-morpholin-4-ium chloride (37 mg, 0.244 mmol) is added. The reaction is heated to 50° C. for 1.5 h and then concentrated in vacuo. The residue is taken up in DMSO-d6 then purified via reverse phase C18 HPLC chromatography eluting with water and acetonitrile containing 0.1% TFA buffer to afford 2-thiazol-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide (58%). MS: 354 (M+H); 1H NMR (300 MHz, CDCl3): δ=2.27 (s, 3H), 7.05 (dt, 1H), 7.32 (s, 1H), 7.32-7.44 (m, 2H), 8.11 (d, 1H), 8.19 (d, 1H), 9.42 (s, 2H), 12.12 (s, 1H).

Workup

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

Sources & evidence

ORD record
ord-64ebc4ded1544221875ac6fc789e9b00
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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