Water → HCID 10217923, compound

HRID 1814880Notes

Reaction equation

HRID 1814880 reaction equation
C(N(CC)C(C)C)(C)C.[Cl:10][C:11]1[CH:33]=[CH:32][C:14]([CH2:15][NH:16][C:17]([C:19]2[C:20](=[O:31])[C:21]3[CH:28]=[C:27]([CH2:29]Cl)[O:26][C:22]=3[N:23]([CH3:25])[CH:24]=2)=[O:18])=[CH:13][CH:12]=1.[OH:34][CH:35]([C:39]1[S:43][C:42]([C:44]#[N:45])=[CH:41][CH:40]=1)[CH2:36][NH:37][CH3:38].O>CN(C=O)C>[Cl:10][C:11]1[CH:33]=[CH:32][C:14]([CH2:15][NH:16][C:17]([C:19]2[C:20](=[O:31])[C:21]3[CH:28]=[C:27]([CH2:29][N:37]([CH2:36][CH:35]([C:39]4[S:43][C:42]([C:44]#[N:45])=[CH:41][CH:40]=4)[OH:34])[CH3:38])[O:26][C:22]=3[N:23]([CH3:25])[CH:24]=2)=[O:18])=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 10126210N-(4-Chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamideHCID 10149046HCID 10149046, compound

Product 1

HCID 10217923HCID 10217923, compoundYield 31.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

N,N-Diisopropylethylamine (0.18 mL) and N-(4-chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide (Example 2, 0.250 g) were added to a solution of rac-5-(1-hydroxy-2-(methylamino)ethyl)thiophene-2-carbonitrile (Preparation 51, 0.188 g) in DMF (15 mL). The reaction mixture was heated to 90° C. for 2 h. The mixture was allowed to cool to room temperature and was poured into water (30 mL). The suspension was filtered and the resulting solid was purified by column chromatography (CH2Cl2/methanol; 98/2) followed by recrystallization from ethyl acetate/methanol to yield 0.111 g of the title compound as a pale yellow solid. Physical characteristics. M.p. 190-195° C. (dec); 1H NMR (400 MHz, DMSO-d6) δ 10.63, 8.56, 7.80, 7.41-7.32, 7.14, 6.88, 6.06, 5.01-4.97, 4.55, 3.92, 3.76, 2.69-2.64, 2.34; 13C NMR (100 MHz, CDCl3) δ 173.7, 164.6, 154.3, 153.2, 150.0, 141.2, 137.4, 137.2, 132.8, 128.9, 128.7, 123.3, 116.9, 114.7, 114.3, 108.5, 106.9, 66.3, 63.9, 54.1, 42.6, 41.8, 37.8; MS (ESI+) m/z 511 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. filtrationThe suspension was filtered
  3. customthe resulting solid was purified by column chromatography (CH2Cl2/methanol; 98/2)
  4. customfollowed by recrystallization from ethyl acetate/methanol

Sources & evidence

ORD record
ord-67cb6b3cf73f4b9c9c7ac81d7ec52377
Source dataset
uspto-grants-2005_04
Patent number
US06878705B2

Reaction notes

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