Diisopropylethylamine → N-[2-Benzyloxy-4-(4,6-bis-((3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-ylamino)-phenyl]-2-hydroxy-6-methoxy-benzamide

HRID 1354822

Reaction equation

HRID 1354822 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:3]=1[C:4]([OH:6])=O.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:46]([O:53][C:54]1[CH:59]=[C:58]([NH:60][C:61]2[N:66]=[C:65]([N:67]3[CH2:72][C@@H:71]([NH:73][C:74]([O:76][C:77]([CH3:80])([CH3:79])[CH3:78])=[O:75])[CH2:70][C@@H:69]([NH:81][C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[CH2:68]3)[N:64]=[C:63]([N:89]3[CH2:94][C@@H:93]([NH:95][C:96]([O:98][C:99]([CH3:102])([CH3:101])[CH3:100])=[O:97])[CH2:92][C@@H:91]([NH:103][C:104]([O:106][C:107]([CH3:110])([CH3:109])[CH3:108])=[O:105])[CH2:90]3)[N:62]=2)[CH:57]=[CH:56][C:55]=1[NH2:111])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CN(C=O)C>[CH2:46]([O:53][C:54]1[CH:59]=[C:58]([NH:60][C:61]2[N:66]=[C:65]([N:67]3[CH2:72][C@@H:71]([NH:73][C:74]([O:76][C:77]([CH3:78])([CH3:79])[CH3:80])=[O:75])[CH2:70][C@@H:69]([NH:81][C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[CH2:68]3)[N:64]=[C:63]([N:89]3[CH2:90][C@@H:91]([NH:103][C:104]([O:106][C:107]([CH3:110])([CH3:109])[CH3:108])=[O:105])[CH2:92][C@@H:93]([NH:95][C:96]([O:98][C:99]([CH3:102])([CH3:101])[CH3:100])=[O:97])[CH2:94]3)[N:62]=2)[CH:57]=[CH:56][C:55]=1[NH:111][C:4](=[O:6])[C:3]1[C:7]([O:11][CH3:12])=[CH:8][CH:9]=[CH:10][C:2]=1[OH:1])[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5915242-Hydroxy-6-methoxybenzoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 588651042-Benzyloxy-N4-(4,6-bis-((3R,5S)-3,5-bis-(tert-butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-yl)-benzene-1,4-diamine

Product 1

HCID 58865371N-[2-Benzyloxy-4-(4,6-bis-((3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-ylamino)-phenyl]-2-hydroxy-6-methoxy-benzamideYield 34.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2-Hydroxy-6-methoxy-benzoic acid (87) (0.067 g=0.4 mmol), iPr2EtN (0.6 mmol) and HBTU (0.44 mmol) were dissolved in DMF (2 mL) and shaken in a sealed vial for 25 min. 2-Benzyloxy-N4-(4,6-bis-((3R,5S)-3,5-bis-(tert-butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-yl)-benzene-1,4-diamine (83) (0.184 g, 0.2 mmol) was added and the mixture was heated to 80° C. for 3 h. LC-MS indicated complete coupling at this point. Upon concentrating, the crude product was dissolved in CHCl3 (4 mL), washed with aqueous sat. NaHCO3 (2×2 mL), water (2×2 mL) and concentrated to dryness. Purification by ISCO (15–100% EtOAc/hexanes) gave the desired product (88) (0.073 g, 0.069 mmol, 34.5% yield). LC-MS (ESI): (exact mass: 1069.56) m/e═1070.9 [M+1]+ (100%).

Workup

  1. concentrationUpon concentrating
  2. dissolutionthe crude product was dissolved in CHCl3 (4 mL)
  3. washwashed with aqueous sat. NaHCO3 (2×2 mL), water (2×2 mL)
  4. concentrationconcentrated to dryness
  5. customPurification by ISCO (15–100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-64886f60c127417c97d33e838b7bbfe5
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Linked notes

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