Diisopropylethylamine → tert-Butyl 2-methyl-1-((S)-1-(2-(N-methyl-3-((4-(piperidin-1-yl)-2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzamido) ethyl) pyrrolidin-2-yl)-1-oxo-5,8,11-trioxa-2-azatetradecan-14-oate

HRID 625455Notes

Reaction equation

HRID 625455 reaction equation
[CH3:1][N:2]([CH2:45][CH2:46][N:47]1[CH2:51][CH2:50][CH2:49][C@H:48]1[C:52](O)=[O:53])[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.[CH3:55][NH:56][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:71]([CH3:74])([CH3:73])[CH3:72])=[O:69].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[CH3:55][N:56]([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:71]([CH3:74])([CH3:73])[CH3:72])=[O:69])[C:52]([C@@H:48]1[CH2:49][CH2:50][CH2:51][N:47]1[CH2:46][CH2:45][N:2]([CH3:1])[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[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]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)=[O:53]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53662991Methylamino-PEG3-t-butyl esterHCID 66588141HCID 66588141, compound

Product 1

HCID 86705970tert-Butyl 2-methyl-1-((S)-1-(2-(N-methyl-3-((4-(piperidin-1-yl)-2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzamido) ethyl) pyrrolidin-2-yl)-1-oxo-5,8,11-trioxa-2-azatetradecan-14-oateYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of (S)-1-(2-(N-methyl-3-((4-(piperidin-1-yl)-2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzamido)ethyl)pyrrolidine-2-carboxylic acid (0.035 mmol, 25.7 mg), tert-butyl 5,8,11-trioxa-2-azatetradecan-14-oate 135c (0.042 mmol, 12.4 mg) and DIEA (0.212 mmol, 27 mg) in DMF (0.15 mL) was added HATU (0.042 mmol, 16 mg). The mixture was stirred at 60° C. for 1 h. The reaction mixture was diluted with ethyl acetate, washed with water (2×), brine (1×), dried and concentrated. 23% of the residue was purified by prep. HPLC to give a yellow solid (4 mg, 37%). MS (ES, m/z): 1002.36 [M+H]+.

Workup

  1. washwashed with water (2×), brine (1×)
  2. customdried
  3. concentrationconcentrated
  4. custom23% of the residue was purified by prep

Sources & evidence

ORD record
ord-267635befdc74bbb9204841bac66725d
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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