HCID 86705988, compound → HCID 86705987, compound

HRID 1408225Notes

Reaction equation

HRID 1408225 reaction equation
[CH3:1][N:2]([CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][C:68]([O:70]C(C)(C)C)=[O:69])[C:3]([C@@H:5]1[CH2:10][O:9][CH2:8][CH2:7][N:6]1[CH2:11][CH2:12][N:13]([CH3:56])[C:14](=[O:55])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21](=[O:54])[NH:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:25][C:24]=2[C:35]2[CH:40]=[C:39]([C:41](=[O:53])[NH:42][C@@H:43]3[C:52]4[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=4)[CH2:46][CH2:45][CH2:44]3)[CH:38]=[CH:37][N:36]=2)[CH:16]=1)=[O:4]>ClCCl.FC(F)(F)C(O)=O>[CH3:1][N:2]([CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][C:68]([OH:70])=[O:69])[C:3]([C@@H:5]1[CH2:10][O:9][CH2:8][CH2:7][N:6]1[CH2:11][CH2:12][N:13]([CH3:56])[C:14](=[O:55])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21](=[O:54])[NH:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:25][C:24]=2[C:35]2[CH:40]=[C:39]([C:41](=[O:53])[NH:42][C@@H:43]3[C:52]4[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=4)[CH2:46][CH2:45][CH2:44]3)[CH:38]=[CH:37][N:36]=2)[CH:16]=1)=[O:4]

Participants

4

Reactant 1

HCID 86705988HCID 86705988, compound

Product 1

HCID 86705987HCID 86705987, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl 2-methyl-1-((S)-4-(2-(N-methyl-3-(4-(piperidin-1-yl)-2-(4-((S)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)benzamido)ethyl)morpholin-3-yl)-1-oxo-5,8,11-trioxa-2-azatetradecan-14-oate Example 242 (100 mg, 0.10 mmol, 1.00 equiv) in dichloromethane (4 mL), trifluoroacetic acid (2 mL). The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. The crude product (80 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 (5% CH3CN up to 28% in 1 min, up to 38% in 6 min); Detector, Waters2545 UvDector 254&270 nm. 8.4 mg product was obtained. This resulted in 8.4 mg (7%) of 2-methyl-1-((S)-4-(2-(N-methyl-3-(4-(piperidin-1-yl)-2-(4-((S)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)benzamido)ethyl)morpholin-3-yl)-1-oxo-5,8,11-trioxa-2-azatetradecan-14-oic acid as a yellow solid. LC-MS (ES, m/z): 962 [M+H]+ H-NMR (300 MHz, CD3OD, ppm): 8.93 (d, J=5.1 Hz, 1H), 8.65 (d, J=9.3 Hz, 1H), 8.39 (s, 1H), 8.24 (s, 1H), 8.14-8.11 (m, 1H), 8.03-8.02 (m, 1H), 7.86-7.84 (m, 2H), 7.76-7.72 (m, 1H), 7.64-7.61 (m, 1H), 7.28-7.25 (m, 1H), 7.18-7.14 (m, 3H), 5.39 (m, 1H), 4.50-4.45 (m, 2H), 4.30-4.20 (m, 1H), 4.09-4.05 (m, 1H), 3.86-3.43 (m, 25H), 3.21 (s, 1H), 3.10-3.08 (m, 3H), 3.00 (s, 1H), 2.91-2.84 (m, 2H), 2.57-2.51 (m, 2H), 2.04-1.79 (m, 10H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product (80 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-3)
  3. waitmobile phase, water with 0.05% TFA and CH3CN (5% CH3CN up to 28% in 1 min
  4. waitup to 38% in 6 min)

Sources & evidence

ORD record
ord-18df3469a7834dad990b8574c0131099
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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