Triethylamine → HCID 67189618, compound

HRID 546170Notes

Reaction equation

HRID 546170 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:16][CH:17]2[CH2:20][O:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[NH2:21][C:22]1[CH:26]=[CH:25][N:24]([CH2:27][C:28]([CH3:31])([OH:30])[CH3:29])[N:23]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:16][CH:17]2[CH2:20][O:19][CH2:18]2)[C:13]([NH:21][C:22]2[CH:26]=[CH:25][N:24]([CH2:27][C:28]([OH:30])([CH3:29])[CH3:31])[N:23]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 67190046HCID 67190046, compound

Product 1

HCID 67189618HCID 67189618, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A reaction of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-oxetan-3-yl-propionic acid (0.18 g, 0.56 mmol), 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in Example 80, 0.1 g, 0.64 mmol), and triethyl amine (0.17 ml, 1.24 mmol) in methylene chloride (15 mL) was cooled to 0° C. To this solution was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.25 g, 0.56 mmol). The reaction was allowed to warm to 25° C. and stirred for 24 h. After this time, the reaction was concentrated in vacuo. Purification on an AnaLogix Intelliflash system (40 g column, 3% methanol/methylene chloride to 5% methanol/methylene chloride) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-oxetan-3-yl-propionamide (0.1 g, 40%) as a 1:1 enantiomeric reaction as a white gummy solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.02 (s, 3H, CH3), 1.04 (s, 3H, CH3), 2.01-2.15 (m, 1H, CH of CH2), 2.32-2.47 (m, 1H, CH of CH2), 2.75-2.91 (m, 1H, CH), 3.31 (s, 3H, SO2CH3), 3.69-3.79 (m, 1H, ArCHCO), 3.85 (s, 2H, NCH2), 4.16-4.30 (m, 2H, 2×OCH of 2×OCH2), 4.47-4.57 (m, 2H, 2×OCH of 2×OCH2), 4.65 (s, 1H, OH), 6.44 (d, J=2.4 Hz, 1H, Ar), 7.52 (d, J=2.4 Hz, 1H, Ar), 7.57 (dd, Jo=8.3 Hz, Jm=1.4 Hz, 1H, Ar), 7.70 (d, Jm=1.4 Hz, 1H, Ar), 8.00 (d, Jo=8.3 Hz, 1H, Ar), 10.77 (s, 1H, NH).

Workup

  1. temperatureto warm to 25° C.
  2. concentrationAfter this time, the reaction was concentrated in vacuo
  3. customPurification on an AnaLogix Intelliflash system (40 g column, 3% methanol/methylene chloride to 5% methanol/methylene chloride)

Sources & evidence

ORD record
ord-5753392224c442b8a3d753e5dee81fdc
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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