Triethylamine → 2-[(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarbonyl)-amino]-4-propyl-thiazole-5-carboxylic acid ethyl ester

HRID 408515Notes

Reaction equation

HRID 408515 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH2:11])=[N:8][C:7]=1[CH2:12][CH2:13][CH3:14])=[O:5])[CH3:2].[O:15]1[C:19]2[CH:20]=[CH:21][C:22]([C:24]3([C:27](O)=[O:28])[CH2:26][CH2:25]3)=[CH:23][C:18]=2[O:17][CH2:16]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:27]([C:24]2([C:22]3[CH:21]=[CH:20][C:19]4[O:15][CH2:16][O:17][C:18]=4[CH:23]=3)[CH2:26][CH2:25]2)=[O:28])=[N:8][C:7]=1[CH2:12][CH2:13][CH3:14])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 824437Ethyl 2-amino-4-propyl-1,3-thiazole-5-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 143496081-(1,3-Dioxaindan-5-yl)cyclopropane-1-carboxylic acid

Product 1

HCID 586098132-[(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarbonyl)-amino]-4-propyl-thiazole-5-carboxylic acid ethyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

2-Amino-4-propyl-thiazole-5-carboxylic acid ethyl ester (0.50 g, 2.3 mmol) and 1-benzo[1,3]dioxol-5-yl-cyclopropanecarboxylic acid (0.48 g, 2.3 mmol) were dissolved in acetonitrile (15 mL) containing triethylamine (0.66 mL, 4.7 mmol). O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 0.89 g, 2.3 mmol) was added and the solution was allowed to stir at 65° C. for four hours. The crude product was evaporated to dryness and purified by column chromatography on silica gel using a gradient of 10-99% ethyl acetate in hexanes. The pure fractions were combined and evaporated to dryness to yield a white solid (0.58 g, 1.4 mmol, 61%). ESI-MS m/z calc. 402.1. found 403.3 (M+1)+. Retention time of 3.78 minutes. 1H NMR (400 MHz, CD3CN) δ 0.84 (t, J=7.4 Hz, 3H), 1.25-1.35 (m, 5H), 1.50-1.68 (m, 4H), 2.91 (t, J=7.5 Hz, 2H), 4.28 (q, J=7.1 Hz, 2H), 6.00 (s, 2H), 6.81 (d, J=7.7 Hz, 1H), 6.95-6.98 (m, 2H), 9.22 (s, 1H).

Workup

  1. customThe crude product was evaporated to dryness
  2. custompurified by column chromatography on silica gel using a gradient of 10-99% ethyl acetate in hexanes
  3. customevaporated to dryness

Sources & evidence

ORD record
ord-8ffab9b19969409f8ed6648a29731f18
Source dataset
uspto-grants-2014_06
Patent number
US08759335B2

Reaction notes

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