Propargyl alcohol → HCID 178432388, compound

HRID 2227163Notes

Reaction equation

HRID 2227163 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH3:12])[N:8]=[CH:7][C:6]([C:13]([NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)=[O:14])=[C:5]2[OH:24].[CH2:25]([OH:28])[C:26]#[CH:27].C(N(CC)CC)C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][NH:15][C:13]([C:6]2[CH:7]=[N:8][C:9]3[C:4]([C:5]=2[OH:24])=[CH:3][C:2]([C:27]#[C:26][CH2:25][OH:28])=[C:11]([CH3:12])[N:10]=3)=[O:14])=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 178432387HCID 178432387, compound

Product 1

HCID 178432388HCID 178432388, compoundYield 35.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-bromo-N-(4-chlorobenzyl)-4-hydroxy-7-methyl[1,8]naphthyridine-3-carboxamide (Ex 2. 0.244 g), propargyl alcohol (0.047 g), triethylamine (0.38 mL) and PdCl2(PPh3)2 (0.023 g) in 3 mL DMF is heated to 90° C. for 2.5 h. The resulting solution is cooled and partitioned between EtOAc and water. The solid which formed is filtered and discarded. The aqueous layer is extracted with EtOAc (3×). The combined organic layers are washed with brine, dried and condensed. The crude product is chromatographed on silica (Biotage flash 40S, eluent 2% MeOH/CH2Cl2 then 3% MeOH/CH2Cl2. Fractions homogeneous by TLC are combined and condensed to yield 0.081 g (35%) of the desired product as a yellow solid. Physical characteristics are as follows: m.p. 279-281° C. (dec.); 1H NMR (DMSO-d6) δ 13.19, 10.12, 8.64, 8.43, 7.38, 5.46, 4.54, 4.40, 2.71; IR (drift) 3194, 3065, 2944, 1645, 1597, 1566, 1522, 1488, 1418, 1357, 1257, 1208, 1015, 851, 809 cm−1; OAMS supporting ions at: ESI+381.9 ESI−379.9; HRMS (FAB) calcd for C20H16ClN3O3 +H1 382.0958, found 382.0960.

Workup

  1. temperatureThe resulting solution is cooled
  2. custompartitioned between EtOAc and water
  3. customThe solid which formed
  4. filtrationis filtered
  5. extractionThe aqueous layer is extracted with EtOAc (3×)
  6. washThe combined organic layers are washed with brine
  7. customdried
  8. customcondensed
  9. customThe crude product is chromatographed on silica (Biotage flash 40S, eluent 2% MeOH/CH2Cl2
  10. customcondensed

Sources & evidence

ORD record
ord-86497e83e48140dd83ad13afc7991e9f
Source dataset
uspto-grants-2002_07
Patent number
US06413958B2

Reaction notes

Loading…