Diisopropylethylamine → 9H-fluoren-9-ylmethyl [6-({2-[(4-{[(tert-butoxycarbonyl)amino]methyl}phenyl)amino]-2-oxoethyl}amino)-6-oxohexyl]carbamate

HRID 1755203Notes

Reaction equation

HRID 1755203 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24](O)=[O:25])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:60][CH2:61][C:62]([NH:64][C:65]1[CH:79]=[CH:78][C:68]([CH2:69][NH:70][C:71](=[O:77])[O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[CH:67][CH:66]=1)=[O:63]>C(Cl)Cl>[C:73]([O:72][C:71]([NH:70][CH2:69][C:68]1[CH:67]=[CH:66][C:65]([NH:64][C:62](=[O:63])[CH2:61][NH:60][C:24](=[O:25])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][NH:18][C:16](=[O:17])[O:15][CH2:14][CH:12]2[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:5]3[C:13]2=[CH:1][CH:2]=[CH:3][CH:4]=3)=[CH:79][CH:78]=1)=[O:77])([CH3:74])([CH3:75])[CH3:76]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27560876-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86718402Tert-butyl [4-(glycylamino)benzyl]carbamate

Product 1

HCID 867184039H-fluoren-9-ylmethyl [6-({2-[(4-{[(tert-butoxycarbonyl)amino]methyl}phenyl)amino]-2-oxoethyl}amino)-6-oxohexyl]carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoic acid (2.66 g, 7.53 mmol, 1.0 eq.) in dry DCM (50 mL) at 0° C. was added N,N-diisopropylethylamine (1.93 g, 15.1 mmol, 2.0 eq) and 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 2.86 g, 7.53 mmol, 1.0 eq.). The mixture was stirred at 0° C. for 30 min and #B119 (2.1 g, 7.53 mmol, 1.0 eq.) was added in one portion. The mixture was stirred at room temperature overnight. The mixture was filtered and solid was washed with DCM and dried in vacuo to afford #B120 (4 g, 86.4%) as a white solid. 1H NMR (400 Hz, DMSO-d6): δ 9.91 (s, 1H), 8.11 (br, 1H), 7.90 (d, 2H), 7.69 (d, 2H), 7.51 (d, 2H), 7.41 (m, 2H), 7.33 (m, 3H), 7.17 (d, 2H), 4.28 (m, 3H), 4.06 (d, 2H), 3.86 (br, 2H), 2.97 (m, 2H), 2.15 (m, 2H), 1.51 (m, 2H), 1.38 (m, 12H); LCMS (Protocol I): m/z 637.1 (M+Na]+, retention time=1.18 minutes.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. filtrationThe mixture was filtered
  3. washsolid was washed with DCM
  4. customdried in vacuo
  5. customto afford #B120 (4 g, 86.4%) as a white solid

Sources & evidence

ORD record
ord-5a8d9cf7abe6476496c317177cb7d7ae
Source dataset
uspto-grants-2015_10
Patent number
US09169264B2

Reaction notes

Loading…