4-Methylmorpholine → N-({4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-N6-(tert-butoxycarbonyl)-D-lysine

HRID 1176074Notes

Reaction equation

HRID 1176074 reaction equation
[Si:1]([O:8][C@H:9]([C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:19][CH:18]=2)[C@@H:13]1[C:31]1[CH:41]=[CH:40][C:34]([O:35][CH2:36][C:37]([OH:39])=O)=[CH:33][CH:32]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:78][CH2:79][C:80]([NH:82][C@@H:83]([C:96]([OH:98])=[O:97])[CH2:84][CH2:85][CH2:86][CH2:87][NH:88][C:89]([O:91][C:92]([CH3:95])([CH3:94])[CH3:93])=[O:90])=[O:81]>CN(C=O)C>[Si:1]([O:8][C@H:9]([C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:28])=[O:29])=[CH:19][CH:18]=2)[C@@H:13]1[C:31]1[CH:41]=[CH:40][C:34]([O:35][CH2:36][C:37]([NH:78][CH2:79][C:80]([NH:82][C@@H:83]([C:96]([OH:98])=[O:97])[CH2:84][CH2:85][CH2:86][CH2:87][NH:88][C:89]([O:91][C:92]([CH3:94])([CH3:95])[CH3:93])=[O:90])=[O:81])=[O:39])=[CH:33][CH:32]=1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68774413{4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acidHCID 86761224Glycyl-N6-(tert-butoxycarbonyl)-D-lysine

Product 1

HCID 86628618N-({4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-N6-(tert-butoxycarbonyl)-D-lysine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

{4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid (Method 8) (15.1 mg, 0.021 mmol) was dissolved in DMF (1 ml, dry). N-methylmorpholine (7 μl, 0.064 mmol) was added and the reaction mixture was stirred at 30° C. for five minutes. TBTU (10.8 mg, 0.034 mmol) was added and the reaction mixture was stirred at the same conditions for 1 hour. Glycyl-N6-(tert-butoxycarbonyl)-D-lysine (10.0 mg 0.033 mmol) was added and the reaction mixture was stirred for 2 hours. The mixture was purified with preparative HPLC on a C8 column. A gradient from 10 to 100% MeCN in a 0.1M NH4OAc buffer was used as eluent. The pure fractions were collected and most of the MeCN was removed under reduced pressure. The residue was lyophilised to give the title compound. M/z: 996.74 (M−1).

Workup

  1. stirringthe reaction mixture was stirred at the same conditions for 1 hour
  2. stirringthe reaction mixture was stirred for 2 hours
  3. customThe mixture was purified with preparative HPLC on a C8 column
  4. customThe pure fractions were collected and most of the MeCN
  5. customwas removed under reduced pressure

Sources & evidence

ORD record
ord-dc964013a83b49909b0645fd3b54fd4b
Source dataset
uspto-grants-2010_11
Patent number
US07842684B2

Reaction notes

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