Dichloromethane → HCID 59128587, compound

HRID 2367823Notes

Reaction equation

HRID 2367823 reaction equation
[K+].[Cl:2][C:3]1[N:7]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[N:6]=[C:5]([C:16]([O-:18])=O)[N:4]=1.CC[N:21]([CH:25]([CH3:27])C)[CH:22]([CH3:24])C.FC(F)(F)[C:30]([OH:32])=[O:31].[C:35]1([C:41]2[CH:46]=[C:45]([CH:47]3CCNCC3)[CH:44]=[CH:43][C:42]=2[NH:53]C(C2NC=C(C#N)N=2)=O)[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]=1.C1CN([P+](Br)(N2[CH2:78][CH2:77][CH2:76]C2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH2:87](Cl)Cl>>[C:77]([O:32][C:30]([N:21]1[CH2:22][CH2:24][CH:47]([C:45]2[CH:44]=[CH:43][C:42]([NH:53][C:16]([C:5]3[N:4]=[C:3]([Cl:2])[N:7]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:13])([CH3:14])[CH3:15])[N:6]=3)=[O:18])=[C:41]([C:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]=3)[CH:46]=2)[CH2:27][CH2:25]1)=[O:31])([CH3:76])([CH3:78])[CH3:87]

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 131727846HCID 131727846, compoundHCID 1785103834-Cyano-1h-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt

Product 1

HCID 59128587HCID 59128587, compoundYield 85%

Procedure

A mixture of 4-(4-{[5-chloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-[1,2,4]-triazole-3-carboxylic acid potassium salt (as prepared above, 35 mg, 0.10 mmol), DIEA (34 μL, 0.10 mmol), 4-(4-amino-3-cyclohex-1-enyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (as prepared in Example 14, step (b), 35.6 mg, 0.100 mmol) and PyBroP (69.9 mg, 0.150 mmol) in DCM (2 mL) was stirred at RT for 12 h. The reaction mixture was diluted with DCM (5 mL) and washed with saturated aqueous NaHCO3 (10 mL) and water (10 mL). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The product was chromatographed on silica (20-40% EtOAc/hexane) to obtain the title compound (52 mg, 85%). 1H-NMR (CDCl3; 400 MHz): δ 9.60 (s, 1H), 8.29 (d, 1H, J=8.4 Hz), 7.18 (dd, 1H, J=8.4, 2.2 Hz), 7.13 (d, 1H, J=2.2 Hz), 5.99 (s, 2H), 5.84 (br s, 1H), 4.18-4.25 (m, 2H), 3.72-3.76 (m, 2H), 2.58-2.67 (m, 2H), 2.51-2.64 (m, 1H), 2.18-2.33 (m, 4H), 1.78-1.92 (m, 6H), 1.55-1.65 (m, 2H), 1.49 (s, 9H), 0.93-0.98 (m, 2H), 0.10 (s, 9H).

Workup

  1. washwashed with saturated aqueous NaHCO3 (10 mL) and water (10 mL)
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe product was chromatographed on silica (20-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-0c7967dffe8542b3b6b730d19cf5dbf3
Source dataset
uspto-grants-2014_04
Patent number
US08697716B2

Reaction notes

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