Diisopropylethylamine → (R)-tert-butyl (2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)(4-(2-(4-(3-((3-carbamoyl-4-((3-methoxyphenyl)amino)-8-methylquinolin-6-yl)sulfonyl)benzamido)phenyl)-1,3-dithiolan-2-yl)butyl)carbamate

HRID 1944963Notes

Reaction equation

HRID 1944963 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:34]([C:37]1[CH:38]=[N:39][C:40]2[C:45]([C:46]=1[NH:47][C:48]1[CH:53]=[CH:52][CH:51]=[C:50]([O:54][CH3:55])[CH:49]=1)=[CH:44][C:43]([S:56]([C:59]1[CH:60]=[C:61]([CH:65]=[CH:66][CH:67]=1)[C:62](O)=[O:63])(=[O:58])=[O:57])=[CH:42][C:41]=2[CH3:68])(=[O:36])[NH2:35].[NH2:69][C:70]1[CH:75]=[CH:74][C:73]([C:76]2([CH2:81][CH2:82][CH2:83][CH2:84][N:85]([CH2:93][C@H:94]([O:107][Si:108]([C:111]([CH3:114])([CH3:113])[CH3:112])([CH3:110])[CH3:109])[C:95]3[CH:104]=[CH:103][C:102]([OH:105])=[C:101]4[C:96]=3[CH:97]=[CH:98][C:99](=[O:106])[NH:100]4)[C:86](=[O:92])[O:87][C:88]([CH3:91])([CH3:90])[CH3:89])[S:80][CH2:79][CH2:78][S:77]2)=[CH:72][CH:71]=1>CN(C1C=CN=CC=1)C.CN1C(=O)CCC1>[Si:108]([O:107][C@H:94]([C:95]1[CH:104]=[CH:103][C:102]([OH:105])=[C:101]2[C:96]=1[CH:97]=[CH:98][C:99](=[O:106])[NH:100]2)[CH2:93][N:85]([CH2:84][CH2:83][CH2:82][CH2:81][C:76]1([C:73]2[CH:74]=[CH:75][C:70]([NH:69][C:62](=[O:63])[C:61]3[CH:65]=[CH:66][CH:67]=[C:59]([S:56]([C:43]4[CH:44]=[C:45]5[C:40](=[C:41]([CH3:68])[CH:42]=4)[N:39]=[CH:38][C:37]([C:34](=[O:36])[NH2:35])=[C:46]5[NH:47][C:48]4[CH:53]=[CH:52][CH:51]=[C:50]([O:54][CH3:55])[CH:49]=4)(=[O:57])=[O:58])[CH:60]=3)=[CH:71][CH:72]=2)[S:80][CH2:79][CH2:78][S:77]1)[C:86](=[O:92])[O:87][C:88]([CH3:91])([CH3:90])[CH3:89])([C:111]([CH3:114])([CH3:113])[CH3:112])([CH3:110])[CH3:109]

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 577632883-[[3-(Aminocarbonyl)-4-[(3-methoxyphenyl)amino]-8-methyl-6-quinolinyl]sulfonyl]benzoic acidHCID 86659090(R)-tert-butyl (4-(2-(4-aminophenyl)-1,3-dithiolan-2-yl)butyl)(2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)carbamate

Product 1

HCID 86659121(R)-tert-butyl (2-((tert-butyldimethylsilyl)oxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)(4-(2-(4-(3-((3-carbamoyl-4-((3-methoxyphenyl)amino)-8-methylquinolin-6-yl)sulfonyl)benzamido)phenyl)-1,3-dithiolan-2-yl)butyl)carbamate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

DMAP (20 mg), HATU (110 mg, 0.29 mmol) and DIEA (0.15 mL, 0.87 mmol) were added to a stirring mixture of 3-[[3-carbamoyl-4-[(3-methoxyphenyl)amino]-8-methylquinolin-6-yl]sulfonyl]benzoic acid (144 mg, 0.29 mmol) and Intermediate 105 (0.18 g, 0.35 mmol) in NMP (3 mL). The reaction mixture was stirred overnight in an 80° C. oil bath and then purified by reverse-phase high performance liquid chromatography (RP-HPLC, acetonitrile/water/0.1% TFA) to provide, after concentration, the title compound as a dark yellow solid (90 mg, 27%). ES/MS calcd. for C60H71N6O10S3Si+ 1159.4. Found m/z=1159.6 (M+H)+.

Workup

  1. custompurified by reverse-phase high performance liquid chromatography (RP-HPLC, acetonitrile/water/0.1% TFA)
  2. customto provide
  3. concentrationafter concentration

Sources & evidence

ORD record
ord-912412a04ad14000b286186eda145e7e
Source dataset
uspto-grants-2013_03
Patent number
US08394829B2

Reaction notes

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