Diisopropylethylamine → (S)-tert-butyl 4-(2-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)-4-(4-(2-(1-(2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)phenylcarbamoyl)phenylthio)phenylcarbamate

HRID 44449Notes

Reaction equation

HRID 44449 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][C:17]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:38])[CH3:37])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH2:72][C:73]1[CH:78]=[CH:77][C:76]([C:79]2[N:80]=[C:81]([C@@H:84]3[CH2:88][CH2:87][CH2:86][N:85]3[C:89](=[O:97])[CH2:90][C:91]3[CH:96]=[CH:95][CH:94]=[CH:93][CH:92]=3)[NH:82][CH:83]=2)=[CH:75][CH:74]=1>CS(C)=O.O>[CH:36]([C:33]1[CH:34]=[CH:35][C:27]2[C:26]([NH:25][C:17]3[CH:18]=[C:19]([C:20](=[O:22])[NH:72][C:73]4[CH:78]=[CH:77][C:76]([C:79]5[N:80]=[C:81]([C@@H:84]6[CH2:88][CH2:87][CH2:86][N:85]6[C:89](=[O:97])[CH2:90][C:91]6[CH:96]=[CH:95][CH:94]=[CH:93][CH:92]=6)[NH:82][CH:83]=5)=[CH:75][CH:74]=4)[CH:23]=[CH:24][C:16]=3[S:15][C:12]3[CH:11]=[CH:10][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[CH:14][CH:13]=3)=[N:31][CH:30]=[N:29][C:28]=2[N:32]=1)([CH3:37])[CH3:38]

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 593768924-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acidHCID 178507416HCID 178507416, compound

Product 1

HCID 136158805(S)-tert-butyl 4-(2-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)-4-(4-(2-(1-(2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)phenylcarbamoyl)phenylthio)phenylcarbamateYield 36%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of the Product from Example 1E (0.16 g, 0.30 mmol) and HATU (0.12 g, 0.316 mmol) in DMSO (5 mL) was added diisopropylethylamine (0.184 mL, 1.05 mmol) followed by the Product from Example 1J (0.115 g, 0.33 mmol). The solution was stirred at ambient temperature for 18 hours, then diluted with water and the crude product was filtered off an purified by combi-flash 12 g column, eluting with 0-10% Methanol in dichloromethane to give a solid (0.092 g, 36%).

Workup

  1. filtrationthe crude product was filtered off
  2. customan purified by combi-flash 12 g column
  3. washeluting with 0-10% Methanol in dichloromethane

Sources & evidence

ORD record
ord-dcb6d69ae0e444d79d1a83f9f5b04b29
Source dataset
uspto-grants-2013_09
Patent number
US08541424B2

Reaction notes

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