4-Methylmorpholine → 3-(3-{1-[2-(2-tert-Butoxycarbonylamino-propionylamino)-3-methyl-butyryl]-pyrrolidin-2-ylmethyl}-benzofuran-2-yl)-propionic acid ethyl ester

HRID 1054008Notes

Reaction equation

HRID 1054008 reaction equation
[C:1]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH2:45]([O:47][C:48](=[O:73])[CH2:49][CH2:50][C:51]1[O:52][C:53]2[CH:72]=[CH:71][CH:70]=[CH:69][C:54]=2[C:55]=1[CH2:56][CH:57]1[CH2:61][CH2:60][CH2:59][N:58]1[C:62](=[O:68])[CH:63]([NH2:67])[CH:64]([CH3:66])[CH3:65])[CH3:46]>CN1C(=O)CCC1.C(OCC)C>[CH2:45]([O:47][C:48](=[O:73])[CH2:49][CH2:50][C:51]1[O:52][C:53]2[CH:72]=[CH:71][CH:70]=[CH:69][C:54]=2[C:55]=1[CH2:56][CH:57]1[CH2:61][CH2:60][CH2:59][N:58]1[C:62](=[O:68])[CH:63]([NH:67][C:11](=[O:13])[CH:9]([NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH3:10])[CH:64]([CH3:66])[CH3:65])[CH3:46]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 671486353-{3-[1-(2-Amino-3-methyl-butyryl)-pyrrolidin-2-ylmethyl]-benzofuran-2-yl}-propionic acid ethyl ester

Product 1

HCID 671489463-(3-{1-[2-(2-tert-Butoxycarbonylamino-propionylamino)-3-methyl-butyryl]-pyrrolidin-2-ylmethyl}-benzofuran-2-yl)-propionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution containing Boc-L-alanine (69 mg, 0.37 mmol) in NMP (3 mL) was treated with HATU (131 mg, 0.34 mmol) followed by NMM (0.1 mL, 0.9 mmol) at ambient temperature. After 10 min, amine 50 (111 mg, 0.28 mmol) in NMP (5 mL) was added in a dropwise fashion. After 5 h, the reaction mixture was diluted with diethyl ether and washed successively with NaHCO3, 1 M HCl, water, and brine. The organic extract was dried over anhydrous Na2SO4, filtered and concentrated to afford 160 mg (quant.) of 51 which was used without further purification. 1H NMR (CDCl3, 300 MHz) δ7.81-7.78 (m, 1H), 7.38-7.36 (m, 1H), 7.28-7.21 (m, 3H), 6.86 (d, J=8.7 Hz, 1H), 5.04 (d, J=6.9 Hz, 1H), 4.61 (dd, J=6.3, 8.7 Hz, 1H), 4.48-4.42 (m, 1H), 4.22 (m, 1H), 4.13 (q, J=6.9 Hz, 2H), 3.73-3.62 (m, 2H), 3.41-3.36 (m, 2H), 3.28 (dd, J=3.0, 13.5 Hz, 1H), 3.11 (app t, J=6.9 Hz, 2H), 2.85-2.73 (m, 4H), 2.38 (app t, J=8.1 Hz, 2H), 2.13-1.98 (m, 2H), 1.80-1.64 (m, 1H), 1.45 (s, 9H), 1.37 (d, J=6.9 Hz, 3H), 1.26 (t, J=7.5 Hz, 3H), 1.03-0.95 (m, 6H) ppm. Mass spectrum: m/z 572 [M+H]+; and, 594 [M+Na]+.

Workup

  1. waitAfter 5 h
  2. washwashed successively with NaHCO3, 1 M HCl, water, and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e3016c1d47044f1c8ea196ea3db08da6
Source dataset
uspto-grants-2016_07
Patent number
US09394249B2

Reaction notes

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