Diisopropylethylamine → HCID 56839792, compound

HRID 889198Notes

Reaction equation

HRID 889198 reaction equation
[NH2:1][CH2:2][C:3]([N:5]([C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]([CH2:14][O:15][C:16]2[C:24]3[N:23]=[C:22]([O:25][CH3:26])[N:21]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[C:20]=3[CH:19]=[CH:18][CH:17]=2)[C:8]=1[Cl:34])[CH3:6])=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:59][C:60]([O:63][C:64]([N:66]1[CH2:70][C@@H:69]([C:71](O)=[O:72])[CH2:68][CH2:67]1)=[O:65])([CH3:62])[CH3:61].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[Cl:34][C:8]1[C:9]([CH2:14][O:15][C:16]2[C:24]3[N:23]=[C:22]([O:25][CH3:26])[N:21]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[C:20]=3[CH:19]=[CH:18][CH:17]=2)=[C:10]([Cl:13])[CH:11]=[CH:12][C:7]=1[N:5]([CH3:6])[C:3](=[O:4])[CH2:2][NH:1][C:71]([C@H:69]1[CH2:68][CH2:67][N:66]([C:64]([O:63][C:60]([CH3:62])([CH3:61])[CH3:59])=[O:65])[CH2:70]1)=[O:72]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1512492(3S)-1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 667603852-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamide

Product 1

HCID 56839792HCID 56839792, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamide (2.00 g, 4 mmol) in anhydrous DMF (12 ml) was treated with HBTU (2.12 g, 5.6 mmol), (S)-1-N-boc-β-proline (0.95 g, 4.4 mmol) and diisopropylethyl amine (2.09 mL, 12 mmol) with stirring at room temperature overnight. To the reaction was added ethyl acetate (200 mL) and the mixture was washed with aqueous saturated sodium bicarbonate (100 mL×3). The organic layer was dried over magnesium sulfate, filtered and evaporated to a tan solid, 2.43 g that was purified by chromatography (silica gel, ethyl acetate and methanol gradient) to afford (S)-tert-butyl 3-(2-((2,4-dichloro-3-((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yloxy)methyl)phenyl)(methyl)amino)-2-oxoethylcarbamoyl)pyrrolidine-1-carboxylate (34) as a tan solid, 1.68 g (60%), that had one peak by LC/MS (+ESI) m/z 697 (M++1) and 711 (M++1) (both ions in the same LC peak), and was pure by 1HNMR (400 MHz, CDCl3) δ 8.60 (m, 1H), 7.60 (m, 1H), 7.48 (m, 1H), 7.28 (m, 1H), 7.19 (m, 1H), 7.04 (m, 1H), 6.93 (m, 1H), 6.81 (m, 2H), 6.50 (m, 1H), 5.67 (s, 2H), 5.28 (s, 2H), 4.22 (s, 3H), 3.81 (m, 1H), 3.50 (m, 4H), 3.25 (m, 4H), 2.91 (m, 1H), 2.08 (m, 3H), 1.44 (s, 9H). 13CNMR (100 MHz, CDCl3) δ 168.2, 156.8, 156.1, 154.3, 149.6, 149.0, 138.4, 138.1, 137.0, 136.5, 135.8, 135.4, 130.1, 129.8, 122.6, 121.7, 120.8, 107.4, 103.1, 79.3, 67.1, 64.3, 60.4, 57.5, 48.6, 47.7, 41.9, 35.9, 30.7, 28.5, 21.0, 19.1, 14.2, 13.7. LN-15495-57.

Workup

  1. washthe mixture was washed with aqueous saturated sodium bicarbonate (100 mL×3)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated to a tan solid, 2.43 g that
  5. customwas purified by chromatography (silica gel, ethyl acetate and methanol gradient)

Sources & evidence

ORD record
ord-508e3a65cd3f4ed68bd18dba92ab448b
Source dataset
uspto-grants-2012_08
Patent number
US08252793B2

Reaction notes

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