1-Hydroxybenzotriazole → HCID 86667484, compound

HRID 2401900Notes

Reaction equation

HRID 2401900 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:5][C:6]1[N:7]=[C:8]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[S:9][C:10]=1[C:11](O)=[O:12].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[O:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH:47]1[O:52][NH2:53]>CN(C)C=O.CCOC(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:5][C:6]1[N:7]=[C:8]([N:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)[S:9][C:10]=1[C:11]([NH:53][O:52][CH:47]1[CH2:48][CH2:49][CH2:50][CH2:51][O:46]1)=[O:12]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68006690HCID 68006690, compound

Product 1

HCID 86667484HCID 86667484, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 4-(3,4-dichlorobenzyl)-2-morpholin-4-yl-1,3-thiazole-5-carboxylic acid.Na (125 mg, 0.316 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (72.8 mg, 0.380 mmol), and 1-hydroxybenzotriazole (51.3 mg, 0.380 mmol) in N,N-dimethylformamide (1.50 mL) was added O-(tetrahydropyran-2-yl)hydroxylamine (55.6 mg, 0.474 mmol). The reaction was stirred at rt for 15 hrs. The mixture was distributed between water and EtOAc, and the aqueous layer was extracted with EtOAc (×2). The combined organic layer was washed with NaHCO3(aq) saturated solution and 10% LiCl(aq) soln (×2), dried over Na2SO4, and concentrated to provide 4-(3,4-dichlorobenzyl)-2-(morpholin-4-yl)-N-(tetrahydro-2H-pyran-2-yloxy)-1,3-thiazole-5-carboxamide as a white solid (153 mg, quantitative). LCMS: (AA) ES+ 472, 474, 476; 1H NMR (400 MHz, CDCl3) δ 7.49-7.43 (d, J=1.9 Hz, 1H), 7.30-7.26 (m, 1H), 7.26-7.17 (m, 1H), 5.01-4.89 (d, J=2.8 Hz, 1H), 4.31-4.21 (m, 2H), 3:96-3.86 (td, J=10.4, 9.1, 2.8 Hz, 1H), 3.80-3.70 (t, J=4.9 Hz, 4H), 3.66-3.56 (m, 1H), 3.51-3.42 (t, J=4.9 Hz, 4H), 1.90-1.73 (m, 3H), 1.69-1.49 (m, 3H).

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (×2)
  2. washThe combined organic layer was washed with NaHCO3(aq) saturated solution and 10% LiCl(aq) soln (×2)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-3ded33f635a14e9b83e78984d2ae8a42
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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