Triethylamine → HCID 68278033, compound

HRID 931517Notes

Reaction equation

HRID 931517 reaction equation
Cl.[CH3:2][C:3]1[O:7][C:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][CH:9]=2)=[N:5][C:4]=1[CH2:17][S:18]([C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH2:29][N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[CH:23][CH:22]=1)(=[O:20])=[O:19].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[N:64]1[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][NH2:71])[CH:65]=1>CN(C)C=O.O>[CH3:2][C:3]1[O:7][C:6]([C:8]2[CH:9]=[CH:10][C:11]([C:12]([NH:71][CH2:70][C:66]3[CH:65]=[N:64][CH:69]=[CH:68][CH:67]=3)=[O:13])=[CH:15][CH:16]=2)=[N:5][C:4]=1[CH2:17][S:18]([C:21]1[CH:22]=[CH:23][C:24]([CH2:27][CH2:28][CH2:29][N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[CH:25][CH:26]=1)(=[O:20])=[O:19]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 68277972HCID 68277972, compound

Product 1

HCID 68278033HCID 68278033, compoundYield 24.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(5-methyl-4-((4-(3-morpholinopropyl)phenylsulfonyl)methyl)oxazol-2-yl)benzoic acid hydrochloride (1.5 g, 2.88 mmol, 1.00 equiv), EDCI (660 mg, 3.46 mmol, 1.20 equiv), HOBt (460 mg, 3.41 mmol, 1.18 equiv), triethylamine (1.16 g, 11.49 mmol, 3.98 equiv) and pyridin-3-ylmethanamine (380 mg, 3.52 mmol, 1.22 equiv) in N,N-dimethylformamide (40 mL) was stirred overnight at 25-30° C. The resulting solution was diluted with 100 mL of water and extracted with 1×100 mL of ethyl acetate. The organic layer was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (550 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-005(Waters)): Column, Xbridge Prep C18, 5 um, 19*150 mm; mobile phase, WATER WITH 0.05% TFA and CH3CN (10% CH3CN up to 30% in 12 min, up to 100% in 1 min); Detector, uv 220/254 nm, to give 400 mg (20%) of 4-(5-methyl-4-((4-(3-morpholinopropyl)phenylsulfonyl)methyl)oxazol-2-yl)-N-(pyridin-3-ylmethyl)benzamide acid trifluoroacetic acid salt as a white solid. LC-MS: (ES, m/z): 575 [M+H]+, 288, 126. 1HNMR (400 MHz, DMSO-d6, ppm): δ 8.79 (m, 1H), 8.70 (d, J=4.8 Hz, 1H), 8.31 (d, J=8.0 Hz, 1H), 7.98 (d, J=8.8 Hz, 2H), 7.92 (d, J=8.4 Hz, 2H), 7.87-7.84 (m, 1H), 7.72 (d, J=8.0 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 4.62 (s, 4H), 3.98-3.94 (m, 2H), 3.64 (s, 2H), 3.42-3.39 (m, 2H), 3.12-3.00 (m, 4H), 2.78-2.73 (m, 2H), 2.09 (s, 3H), 2.00-1.92 (m, 2H).

Workup

  1. extractionextracted with 1×100 mL of ethyl acetate
  2. washThe organic layer was washed with 3×50 mL of brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product (550 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-005(Waters))
  6. waitup to 100% in 1 min)

Sources & evidence

ORD record
ord-0b981851cec942888372d8bceca0df5f
Source dataset
uspto-grants-2016_03
Patent number
US09296732B2

Reaction notes

Loading…