Diisopropylethylamine → HCID 178491113, compound

HRID 25238Notes

Reaction equation

HRID 25238 reaction equation
[I-].ClC1C=CC=C[N+]=1C.[CH3:10][O:11][C:12]1[CH:23]=[CH:22][C:15]([C:16]([NH:18][C:19](=[O:21])[CH3:20])=S)=[CH:14][CH:13]=1.Cl.Cl.[NH2:26][CH:27]([CH2:40][CH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1)[C:28]([NH:30][C:31]1([C:38]#[N:39])[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]1)=[O:29].C(N(CC)C(C)C)(C)C>ClCCl>[C:19]([N:18]=[C:16]([NH:26][CH:27]([CH2:40][CH:41]1[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]1)[C:28]([NH:30][C:31]1([C:38]#[N:39])[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]1)=[O:29])[C:15]1[CH:22]=[CH:23][C:12]([O:11][CH3:10])=[CH:13][CH:14]=1)(=[O:21])[CH3:20]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 13835614N-[(4-Methoxyphenyl)carbonothioyl]acetamideHCID 225663392-amino-N-(-4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexylpropionamide bis hydrochloride salt

Product 1

HCID 178491113HCID 178491113, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Chloro-N-methylpyridinium iodide (660 mg, 2.58 mmol), was added to a solution of N-(4-methoxy-thiobenzoyl)acetamide (420 mg, 2.01 mmol), 2-amino-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide bis hydrochloride salt (730 mg, 2.00 mmol), and N,N-diisopropylethylamine (1.05 mL, 6.02 mmol) in dichloromethane (8.0 mL). The reaction mixture was stirred at room temperature for 2 h, then diluted with dichloromethane (100 mL)and washed with 2×150 mL of saturated sodium bicarbonate. The organic phase was dried (MgSO4) and concentrated. The resulting residue was chromatographed over 100 g of flash silica first using EtOAc, then dichloromethane/methanol 9:1 as the eluant to provide the desired product as an off white solid (377 mg, 40%). 1H NMR (400 MHz, DMSO-d6) δ 0.70-0.90 (m, 2H), 1.00-1.30 (m, 4H), 1.35-1.65 (m, 8H), 1.72 (s, 3H), 1.85-2.20 (m, 6H), 2.48-2.60 (m, 1H), 3.78 (s, 3H), 4.20-4.35 (m, 1H), 6.95-6.99 (m, 2 H), 7.33 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H). MS, m/z 468=M+1.

Workup

  1. washwashed with 2×150 mL of saturated sodium bicarbonate
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated
  4. customThe resulting residue was chromatographed over 100 g of flash silica first using EtOAc

Sources & evidence

ORD record
ord-cd0d0a9d86e2473c9942357e0e93e3c5
Source dataset
uspto-grants-2005_02
Patent number
US06858623B2

Reaction notes

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