Diisopropylethylamine → tert-butyl (2S)-2-{[4-(methylamino)phenyl]carbonylamino}-4-{N-[2-(2-{2-[2-(2-{2-[2-(4-{5-[(N-morpholin-4-ylcarbamoyl)amino]-4-oxoindeno[3,2-c]pyrazol-3-yl}phenoxy)acetylamino]ethoxy}ethoxy)ethoxy]ethoxy}ethoxy)ethyl]carbamoyl}butanoa te

HRID 720868Notes

Reaction equation

HRID 720868 reaction equation
[N:1]1([NH:7][C:8]([NH:10][C:11]2[C:16]3[C:17](=[O:34])[C:18]4[C:19](=[N:20][NH:21][C:22]=4[C:23]4[CH:33]=[CH:32][C:26]([O:27][CH2:28][C:29]([OH:31])=O)=[CH:25][CH:24]=4)[C:15]=3[CH:14]=[CH:13][CH:12]=2)=[O:9])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[NH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][O:50][CH2:51][CH2:52][NH:53][C:54]([CH2:56][CH2:57][C@H:58]([NH:66][C:67]([C:69]1[CH:74]=[CH:73][C:72]([NH:75][CH3:76])=[CH:71][CH:70]=1)=[O:68])[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[O:55].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:76][NH:75][C:72]1[CH:73]=[CH:74][C:69]([C:67]([NH:66][C@@H:58]([CH2:57][CH2:56][C:54](=[O:55])[NH:53][CH2:52][CH2:51][O:50][CH2:49][CH2:48][O:47][CH2:46][CH2:45][O:44][CH2:43][CH2:42][O:41][CH2:40][CH2:39][O:38][CH2:37][CH2:36][NH:35][C:29](=[O:31])[CH2:28][O:27][C:26]2[CH:32]=[CH:33][C:23]([C:22]3[NH:21][N:20]=[C:19]4[C:15]5[CH:14]=[CH:13][CH:12]=[C:11]([NH:10][C:8](=[O:9])[NH:7][N:1]6[CH2:6][CH2:5][O:4][CH2:3][CH2:2]6)[C:16]=5[C:17](=[O:34])[C:18]=34)=[CH:24][CH:25]=2)[C:59]([O:61][C:62]([CH3:65])([CH3:63])[CH3:64])=[O:60])=[O:68])=[CH:70][CH:71]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66933864HCID 66933864, compoundHCID 1785259502-(4-(5-[(morpholin-4-ylamino)carbonylamino]-4-oxoindeno[3,2-c]pyrazol-3-yl}phenoxy)acetic Acid

Product 1

HCID 178482177tert-butyl (2S)-2-{[4-(methylamino)phenyl]carbonylamino}-4-{N-[2-(2-{2-[2-(2-{2-[2-(4-{5-[(N-morpholin-4-ylcarbamoyl)amino]-4-oxoindeno[3,2-c]pyrazol-3-yl}phenoxy)acetylamino]ethoxy}ethoxy)ethoxy]ethoxy}ethoxy)ethyl]carbamoyl}butanoa te

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Compound 25 (0.60 g, 1 mmol) and compound 26 (0.46 g, 1 mmol) were dissolved in 10 ml DMF and HBTU (0.7 g, 1.8 mmol) was added as a solid followed by DIEA (1.0 ml, 5.7 mmol). The reaction mixture was stirred at room temperature overnight, diluted with EtOAc and the organic phase washed with 0.5N NaOH, brine, dried over MgSO4, filtered and concentrated to an oil. This oil was purified by flash silica chromatography (10 to 20% MeOH/EtOAc) to give a yellow foam (0.65 g, 0.62 mmol, 62%, compound 28).

Workup

  1. washthe organic phase washed with 0.5N NaOH, brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to an oil
  5. customThis oil was purified by flash silica chromatography (10 to 20% MeOH/EtOAc)

Sources & evidence

ORD record
ord-e02df997e5cc496a85184447edf42f8d
Source dataset
uspto-grants-2006_11
Patent number
US07135550B2

Reaction notes

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