Dimethylformamide → (1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3h-imidazol-4-yl}-6-methyl-6,7-dihydro-5h-dibenzo[c,e]azepin-3-yl)-1h-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 79652

Reaction equation

HRID 79652 reaction equation
[CH3:1][O:2][C:3](=[O:5])[NH2:4].[NH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11]1[NH:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]3[C:25]4[CH:26]=[CH:27][C:28]([C:30]5[NH:31][C:32]([CH:35]6[CH2:39][CH2:38][CH2:37][NH:36]6)=[N:33][CH:34]=5)=[CH:29][C:24]=4[CH2:23][N:22]([CH3:40])[CH2:21][C:20]=3[CH:41]=2)=[CH:13][N:12]=1.[CH3:42][O:43][C:44]([NH:46][C@H:47]([C:51]([OH:53])=O)[CH:48]([CH3:50])[CH3:49])=[O:45].CN(C(ON1N=NC2[CH:65]=[CH:66][CH:67]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:78](N(C(C)C)CC)(C)C.CN([CH:90]=[O:91])C>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:5])[NH:4][CH:78]([C:90]([N:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11]1[NH:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]3[C:25]4[CH:26]=[CH:27][C:28]([C:30]5[NH:31][C:32]([CH:35]6[CH2:39][CH2:38][CH2:37][N:36]6[C:51](=[O:53])[CH:47]([NH:46][C:44]([O:43][CH3:42])=[O:45])[CH:48]([CH3:49])[CH3:50])=[N:33][CH:34]=5)=[CH:29][C:24]=4[CH2:23][N:22]([CH3:40])[CH2:21][C:20]=3[CH:41]=2)=[CH:13][N:12]=1)=[O:91])[CH:66]([CH3:65])[CH3:67]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 11722Methyl CarbamateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 666205783,9-bis-[2-(pyrrolidin-2-yl)-3H-imidazol-4-yl]-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepine

Product 1

HCID 66620472(1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3h-imidazol-4-yl}-6-methyl-6,7-dihydro-5h-dibenzo[c,e]azepin-3-yl)-1h-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester: To the solution of 3,9-bis-[2-(pyrrolidin-2-yl)-3H-imidazol-4-yl]-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepine (25 mg, 0.035 mmol) and MeOCO-Val-OH (13 mg, 0.074 mmol) in DMF (1.2 ml) was added HATU (28 mg, 0.074 mmol), followed by diisopropylethylamine (61 μl, 0.35 mmol). The mixture was stirred for 90 minutes and was diluted with EtOAc. The organic phase was washed with 1 N NaOH solution, water, and brine, and was dried with sodium sulfate. Concentration and purification by HPLC (0.1% TFA/CH3CN/0.1% TFA/H2O) gave (1-{2-[5-(9-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl]-2-methyl-propyl)-carbamic acid methyl ester (24 mg). m/z: 794.3 (M+H)+, 397.8 (M+2H)+/2. 1H NMR (CD3OD, 300 MHz) δ 8.0-7.9 (8 H, m), 5.27 (2 H, m), 4.3-4.2 (2 H, m), 4.2-3.8 (8 H, m), 3.66 (6 H, s), 3.08 (3 H, s), 2.7-2.5 (2 H, m), 2.4-1.9 (8 H, m), 0.94-0.90 (12 H, m).

Workup

  1. washThe organic phase was washed with 1 N NaOH solution, water, and brine
  2. dry with materialwas dried with sodium sulfate
  3. concentrationConcentration and purification by HPLC (0.1% TFA/CH3CN/0.1% TFA/H2O)

Sources & evidence

ORD record
ord-4156575b80f04585b4d71c4eb6460ce2
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Linked notes

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