1-[2-(2-Hydroxyethoxy)ethyl]piperazine → HCID 56966012, compound

HRID 625482Notes

Reaction equation

HRID 625482 reaction equation
[CH3:1][N:2]([CH2:45][C:46](O)=[O:47])[C:3](=[O:44])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10](=[O:43])[NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:14][C:13]=2[C:24]2[CH:29]=[C:28]([C:30](=[O:42])[NH:31][C@@H:32]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[CH2:35][CH2:34][CH2:33]3)[CH:27]=[CH:26][N:25]=2)[CH:5]=1.CCN=C=NCCCN(C)C.Cl.[N:61]1([CH2:67][CH2:68][O:69][CH2:70][CH2:71][OH:72])[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>ClCCl.CN(C)C1C=CN=CC=1>[OH:72][CH2:71][CH2:70][O:69][CH2:68][CH2:67][N:61]1[CH2:66][CH2:65][N:64]([C:46](=[O:47])[CH2:45][N:2]([CH3:1])[C:3](=[O:44])[C:4]2[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[CH:14][C:13]=3[C:24]3[CH:29]=[C:28]([C:30](=[O:42])[NH:31][C@@H:32]4[C:41]5[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=5)[CH2:35][CH2:34][CH2:33]4)[CH:27]=[CH:26][N:25]=3)=[O:43])[CH:5]=2)[CH2:63][CH2:62]1

Participants

6

Reactant 3

HCID 1394361-[2-(2-Hydroxyethoxy)ethyl]piperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86705989HCID 86705989, compound

Product 1

HCID 56966012HCID 56966012, compoundYield 23.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Into a 100-mL round-bottom flask, was placed a solution of (S)-2-(N-methyl-3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)benzamido)acetic acid (200 mg, 0.31 mmol, 1.00 equiv) in dichloromethane (10 mL), EDC.HCl (113 mg, 0.59 mmol, 1.90 equiv), 4-dimethylaminopyridine (80 mg, 0.65 mmol, 2.11 equiv), 2-(2-(piperazin-1-yl)ethoxy)ethanol (103 mg, 0.59 mmol, 1.91 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 30 mL of dichloromethane. The resulting mixture was washed with 2×30 mL of NH4Cl.aq. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (200 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 (23% CH3CN up to 34% in 6 min); Detector, Waters2545 UvDector 254&270 nm. 57.6 mg product was obtained. This resulted in 57.6 mg (23%) of (S)—N1-(2-(4-(2-(2-hydroxyethoxy)ethyl)piperazin-1-yl)-2-oxoethyl)-N1-methyl-N3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide as a yellow solid. LC-MS (ES, m/z): 802 [M+H]+ H-NMR (300 MHz, DMSO, ppm): 12.38 (s, 1H), 9.94 (s, 1H), 9.21˜9.19 (d, J=8.4 Hz, 1H), 8.95˜8.90 (m, 1H), 8.00˜7.95 (m, 2H), 7.87˜7.84 (m, 3H), 7.67˜7.54 (m, 3H), 7.30˜7.13 (m, 5H), 5.27˜5.25 (m, 1H), 3.79˜3.69 (m, 3H), 3.57˜3.11 (m, 16H), 3.00˜2.92 (m, 4H), 2.78 (s, 2H), 2.00 (s, 2H), 1.85˜1.79 (m, 6H), 1.55 (s, 2H).

Workup

  1. customInto a 100-mL round-bottom flask, was placed
  2. washThe resulting mixture was washed with 2×30 mL of NH4Cl
  3. dry with materialThe mixture was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-3)
  6. waitmobile phase, water with 0.05% TFA and CH3CN (23% CH3CN up to 34% in 6 min)

Sources & evidence

ORD record
ord-917e30a2526a4aab878cff0fe68dc97b
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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