Ethoxalyl chloride → HCID 86715507, compound

HRID 2284595Notes

Reaction equation

HRID 2284595 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[N:16][C:17]([CH2:20][NH2:21])=[CH:18][CH:19]=3)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1[CH3:22].CCN(C(C)C)C(C)C.Cl[C:33](=[O:39])[C:34]([O:36][CH2:37][CH3:38])=[O:35]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[N:16][C:17]([CH2:20][NH:21][C:33](=[O:39])[C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:18][CH:19]=3)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1[CH3:22]

Participants

5

Reactant 3

HCID 20884Ethoxalyl chlorideHCID 81531DiisopropylethylamineHCID 86715505HCID 86715505, compound

Product 1

HCID 86715507HCID 86715507, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of (2′-(4-fluoro-3-methylphenyl)-[3,3′-bipyridin]-6-yl)methanamine (2.0 g) in CH2Cl2 (30 mL) under nitrogen atmosphere, i-Pr2NEt (2.6 mL) was added and stirred for 10 min at room temperature. Ethyl 2-chloro-2-oxoacetate (1.1 mL) as neat was added dropwise for 10 min. After 1 h, the reaction mixture was concentrated, partitioned between CH2Cl2 (75 mL)/aq. NaCl (20 mL) and the organic layer was separated. Usual workup and purification by chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g and 50-100% EtOAc/hexanes as an elutant) provided 1.4 g of ethyl 2-(((2′-(4-fluoro-3-methylphenyl)-[3,3′-bipyridin]-6-yl)methyl)amino)-2-oxoacetate as an off-white solid. 1H NMR (300 MHz, DMSO-d6): δ 9.41 (t, J=6.2 Hz, 1H), 8.67 (dd, J=4.7, 1.7 Hz, 1H), 8.30 (dd, J=2.4, 0.9 Hz, 1H), 7.87 (dd, J=7.8, 1.7 Hz, 1H), 7.56 (dd, J=8.1, 2.3 Hz, 1H), 7.49 (dd, J=7.8, 4.8 Hz, 1H), 7.29-7.22 (m, 2H), 6.98 (dd, J=7.7, 1.1 Hz, 2H), 4.42 (d, J=6.1 Hz, 2H), 4.23 (q, J=7.1 Hz, 2H), 2.21-2.09 (m, 3H), 1.26 (t, J=7.1 Hz, 3H).

Workup

  1. waitAfter 1 h
  2. concentrationthe reaction mixture was concentrated
  3. custompartitioned between CH2Cl2 (75 mL)/aq
  4. customNaCl (20 mL) and the organic layer was separated
  5. customUsual workup and purification by chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g and 50-100% EtOAc/hexanes as an elutant)

Sources & evidence

ORD record
ord-39c376106c9a45b3857134673e08bb64
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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