Dichloromethane → HCID 59128587, compound

HRID 1428056Notes

Reaction equation

HRID 1428056 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-d674e60292784983a61d56955936522e
Source dataset
uspto-grants-2015_01
Patent number
US08933091B2

Reaction notes

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