4-Methylmorpholine → 4-Tert-butyl-2-(4-methyl-benzoylamino)-4h-pyrrolo[2,3-d]thiazole-6-carboxylic acid(thiazol-2-ylmethyl)-amide

HRID 1594226Notes

Reaction equation

HRID 1594226 reaction equation
[C:1]([N:5]1[C:9]2[N:10]=[C:11]([NH:13][C:14](=[O:22])[C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)[S:12][C:8]=2[C:7]([C:23](O)=[O:24])=[CH:6]1)([CH3:4])([CH3:3])[CH3:2].Cl.[S:27]1[CH:31]=[CH:30][N:29]=[C:28]1[CH2:32][NH2:33].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>O.CN(C)C=O>[S:27]1[CH:31]=[CH:30][N:29]=[C:28]1[CH2:32][NH:33][C:23]([C:7]1[C:8]2[S:12][C:11]([NH:13][C:14](=[O:22])[C:15]3[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=3)=[N:10][C:9]=2[N:5]([C:1]([CH3:3])([CH3:4])[CH3:2])[CH:6]=1)=[O:24]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 42614216(1,3-Thiazol-2-yl)methanamine hydrochlorideHCID 590012694-Tert-Butyl-2-(4-methyl-benzoylamino)-4H-pyrrolo[2,3-d]thiazole-6-carboxylic acid

Product 1

HCID 590013104-Tert-butyl-2-(4-methyl-benzoylamino)-4h-pyrrolo[2,3-d]thiazole-6-carboxylic acid(thiazol-2-ylmethyl)-amideYield 68.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Anhydrous N,N-dimethylformamide (30 ml) was added to a mixture of 4-tert-butyl-2-(4-methyl-benzoylamino)-4H-pyrrolo[2,3-d]thiazole-6-carboxylic acid (1.1g, 2.9 mmol), C-thiazol-2-yl-methylamine hydrochloride (0.5 g, 3.3 mmol), 1-hydroxy-7-azabenzotriazole (HOAt, 0.4 g, 2.9 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC, 0.9 g, 4.4 mmol), and 4-methyl-morpholine (NMM, 0.8 ml, 7.2 mmol). The resulting solution was stirred at ambient temperature, under N2 blanket, for 15 hours, then slowly poured into 300 ml of rapidly stirred water. Precipitated solid was isolated by filtration, flash chromatographed (silica gel, 100% EtOAc), and then crystallized from ethyl acetate/hexanes to afford 0.9 g (68%) of the product as fine white crystalline powder, mp. 245-246° C. (decomp.). 1H NMR (d6-DMSO): δ 1.72 ppm, s, 9H, 2.40 ppm, s, 3H, 4.73 ppm, d, j=6.0 Hz, 2H, 7.35 ppm, d, j=7.8 Hz, 2H; 7.63 ppm, d, j=3.3 Hz, 1H, 7.74 ppm, d, j=3.3 Hz, 1H, 7.85 ppm, s, 1H, 8.03 ppm, d, j=8.1 Hz, 2H, 8.92 ppm, t, j=6.0 Hz, 1H, 12.49 ppm, s, 1H. MS: M+H=454.

Workup

  1. customPrecipitated solid
  2. customwas isolated by filtration, flash
  3. customchromatographed (silica gel, 100% EtOAc)
  4. customcrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4ad9c4473ebe407c837637e170447972
Source dataset
uspto-grants-2007_11
Patent number
US07300949B2

Reaction notes

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