Diisopropylethylamine → HCID 178429007, compound

HRID 1907152Notes

Reaction equation

HRID 1907152 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([NH:22][C@@H:23]([C:25]([NH:27][CH2:28][C@@H:29]([NH2:37])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:26])[CH3:24])=[O:21])[CH2:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([OH:18])=[CH:13][C:12]=1[CH3:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:38]([O:45][C:46]([NH:48][C:49](N1C=CC=N1)=[N:50][C:51]([O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:52])=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(N(CC)C(C)C)(C)C>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([NH:22][C@@H:23]([C:25]([NH:27][CH2:28][C@@H:29]([NH:37]/[C:49](/[NH:50][C:51]([O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:52])=[N:48]\[C:46]([O:45][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:47])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:26])[CH3:24])=[O:21])[CH2:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([OH:18])=[CH:13][C:12]=1[CH3:19])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 3563804Phenylmethyl N-((((phenylmethoxy)carbonyl)amino)-1H-pyrazol-1-ylmethylene)carbamateHCID 67342806HCID 67342806, compound

Product 1

HCID 178429007HCID 178429007, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosyl-N-[(2S)-2-amino-3-phenylpropyl]-D-alaninamide (330 mg, 0.64 mmol) from preparation 33 in THF (5 mL) was added N,N′-Bis(benzyloxycarbonyl)-1H-pyrazole-1-carboxamidine (268 mg, 0.71 mmol) and N,N-diisopropylethylamine (173 uL, 0.97 mmol). The reaction was stirred for 2 hours at 60° C. and then quenched by the addition of water (5 mL). The mixture was extracted with ethyl acetate (10 mL), the extract was dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 25% ethyl acetate in heptane as eluent increasing to 33%) to afford the title compound as a colourless oil in 81% yield, 430 mg. 1H NMR (400 MHz, MeOH-d4) δ : 1.05 (d, 3H), 1.28 (s, 9H), 2.22 (s, 6H), 2.73-3.11 (m, 4H), 3.41-3.52 (m, 1H), 3.95-4.23 (m, 2H), 4.38-4.59 (m, 2H), 4.98-5.28 (m, 4H), 6.45 (s, 2H), 7.09-7.46 (m, 15H). LRMS APCI m/z 823 [MH]+

Workup

  1. customquenched by the addition of water (5 mL)
  2. extractionThe mixture was extracted with ethyl acetate (10 mL)
  3. dry with materialthe extract was dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (silica, 25% ethyl acetate in heptane as eluent increasing to 33%)

Sources & evidence

ORD record
ord-6876d9710c214cb19879aada1f188dcf
Source dataset
uspto-grants-2013_12
Patent number
US08598123B2

Reaction notes

Loading…