1-[2-(2-Hydroxyethoxy)ethyl]piperazine → HCID 86705985, compound

HRID 1408224Notes

Reaction equation

HRID 1408224 reaction equation
[CH3:1][N:2]([CH2:54][CH2:55][O:56][CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][C:65](O)=[O:66])[C:3](=[O:53])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([S:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19](=[O:52])[NH:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:23][C:22]=3[C:33]3[CH:38]=[C:37]([C:39](=[O:51])[NH:40][C@@H:41]4[C:50]5[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=5)[CH2:44][CH2:43][CH2:42]4)[CH:36]=[CH:35][N:34]=3)[CH:14]=2)[CH:6]=1.[N:68]1([CH2:74][CH2:75][O:76][CH2:77][CH2:78][OH:79])[CH2:73][CH2:72][NH:71][CH2:70][CH2:69]1>ClCCl.C(OCC)(=O)C>[OH:79][CH2:78][CH2:77][O:76][CH2:75][CH2:74][N:68]1[CH2:73][CH2:72][N:71]([C:65](=[O:66])[CH2:64][CH2:63][O:62][CH2:61][CH2:60][O:59][CH2:58][CH2:57][O:56][CH2:55][CH2:54][N:2]([CH3:1])[C:3](=[O:53])[CH2:4][C:5]2[CH:6]=[C:7]([S:11][CH2:12][C:13]3[CH:14]=[C:15]([CH:16]=[CH:17][CH:18]=3)[C:19]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:23][C:22]=3[C:33]3[CH:38]=[C:37]([CH:36]=[CH:35][N:34]=3)[C:39]([NH:40][C@@H:41]3[C:50]4[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=4)[CH2:44][CH2:43][CH2:42]3)=[O:51])=[O:52])[CH:8]=[CH:9][CH:10]=2)[CH2:70][CH2:69]1

Participants

5

Reactant 2

HCID 1394361-[2-(2-Hydroxyethoxy)ethyl]piperazineHCID 86705986HCID 86705986, compound

Product 1

HCID 86705985HCID 86705985, compoundYield 14.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

This compound was prepared according to the procedure described for the synthesis of Example 231 substituting Example 235 in place of 231a. A solution of (S)-3-methyl-2-oxo-1-(3-(3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)benzylthio)phenyl)-6,9,12-trioxa-3-azapentadecan-15-oic acid (120 mg, 0.13 mmol, 1.00 equiv) in dichloromethane (5 mL), 2-(2-(piperazin-1-yl)ethoxy)ethanol (33.7 mg, 0.19 mmol, 1.50 equiv), N-(3-dimethylaminopropyl)-Ni−-ethylcarbodiimide hydrochloride (49.7 mg, 0.26 mmol, 2.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 2×20 mL of brine. The mixture was dried over sodium sulfate and concentrated under vacuum. The crude product (100 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-3): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (30% CH3CN up to 42% in 6 min); Detector, Waters2545 UvDector 254&270 nm. 20 mg product was obtained. This resulted in 20 mg (14%) of (S)-2-(2-(3-((3-(15-(4-(2-(2-hydroxyethoxy)ethyl)piperazin-1-yl)-3-methyl-2,15-dioxo-6,9,12-trioxa-3-azapentadecyl)phenylthio)methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)isonicotinamide as a yellow solid. LC-MS (ES, m/z): 1084 [M+H]+ H-NMR (300 MHz, DMSO, ppm): 12.19 (s, 1H), 9.65 (s, 1H), 9.19 (d, J=8.4 Hz, 1H), 8.91 (d, J=15.1 Hz, 1H), 8.28 (d, J=12.9 Hz, 2H), 7.90 (s, 1H), 7.85 (d, J=4.8 Hz, 1H), 7.75 (d, J=7.5 Hz, 1H), 7.44˜7.57 (m, 8H), 7.10˜7.22 (m, 8H), 7.01 (d, J=2.4 Hz, 1H), 5.25 (d, J=6.6 Hz, 1H), 4.34 (s, 1H), 4.05 (s, 1H), 3.50˜3.80 (m, 8H), 3.30˜3.40 (m, 8H), 1.95 (s, 2H), 1.80 (s, 2H), 1.90˜2.10 (m, 2H), 1.50˜1.80 (m, 8H).

Workup

  1. customThis compound was prepared
  2. washThe resulting mixture was washed with 2×20 mL of brine
  3. dry with materialThe mixture was dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product (100 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-3)
  6. waitmobile phase, water with 0.05% TFA and CH3CN (30% CH3CN up to 42% in 6 min)

Sources & evidence

ORD record
ord-3302414e93ab4b678ad0d2c374a37d61
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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