1,2-Dichloroethane → HCID 131735604, compound

HRID 527753Notes

Reaction equation

HRID 527753 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:14])[C@@H:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.N1C2C(=NC=CC=2)N(O)N=1.Cl.[NH2:30][C@H:31]([C:51]([N:53]1[C@H:57]([C:58](=[O:70])[NH:59][C@H:60]2[C:69]3[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=3)[CH2:63][CH2:62][CH2:61]2)[CH2:56][Si:55]([CH3:72])([CH3:71])[CH2:54]1)=[O:52])[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]#[C:40][C:41]2[CH:50]=[CH:49][C:44]([C:45]([O:47][CH3:48])=[O:46])=[CH:43][CH:42]=2)=[CH:35][CH:34]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]([CH3:14])[C@@H:9]([CH3:13])[C:10]([NH:30][C@H:31]([C:51]([N:53]1[C@H:57]([C:58](=[O:70])[NH:59][C@H:60]2[C:69]3[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=3)[CH2:63][CH2:62][CH2:61]2)[CH2:56][Si:55]([CH3:72])([CH3:71])[CH2:54]1)=[O:52])[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]#[C:40][C:41]2[CH:42]=[CH:43][C:44]([C:45]([O:47][CH3:48])=[O:46])=[CH:49][CH:50]=2)=[CH:35][CH:34]=1)=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 131735605HCID 131735605, compound

Product 1

HCID 131735604HCID 131735604, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of (S)-2-((tert-butoxycarbonyl)(methyl)amino)propanoic acid (34 mg, 0.17 mmol) in DMF (2 mL) were added EDC (41 mg, 0.22 mmol) and 3H-[1,2,3]-triazolo[4,5-b]pyridin-3-ol (17 mg, 0.13 mmol), followed by a solution of methyl 4-((4-((S)-2-amino-3-((R)-3,3-dimethyl-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,3-azasilolidin-1-yl)-3-oxopropyl)phenyl)ethynyl)benzoate HCl salt (80 mg, 0.13 mmol) in DMF (2 mL) and DIEA (0.07 mL, 0.38 mmol). The reaction mixture was stirred at rt for 1 h and diluted with ethyl acetate and brine. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated in vacuo to give the title compound as a yellow solid (85 mg, 86%). 1H NMR (CDCl3) δ 8.10-7.91 (m, 2H), 7.63-7.50 (m, 2H), 7.40 (d, J=8.1 Hz, 2H), 7.24-7.00 (m, 5.5H), 6.56 (d, J=8.6 Hz, 0.5H), 5.26-5.06 (m, 2.5H), 4.11 (q, J=7.0 Hz, 0.5H), 3.92 (s, 3H), 3.21-2.55 (m, 6H), 2.49 (s, 3H), 2.14-1.70 (m, 5H), 1.47 (s, 9H), 1.31-0.90 (m, 5H), 0.52-0.19 (m, 6H); MS(ESI+) m/z 779.6 (M+H)+.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-45320e0e14bb4688bfa59b122d4921fe
Source dataset
uspto-grants-2016_05
Patent number
US09345740B2

Reaction notes

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