Ammonia → HCID 90338476, compound

HRID 1508782Notes

Reaction equation

HRID 1508782 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]3[CH2:14][CH2:15][CH2:16][C:11]3=[C:10]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([CH3:29])([CH3:28])[C:25]([OH:27])=O)=[CH:20][CH:19]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[NH3:36].CO>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]3[CH2:14][CH2:15][CH2:16][C:11]3=[C:10]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([C:24]([CH3:28])([CH3:29])[C:25]([NH2:36])=[O:27])=[CH:22][CH:23]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 887MethanolHCID 65578Oxalyl chlorideHCID 90338527HCID 90338527, compound

Product 1

HCID 90338476HCID 90338476, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

An 250-mL round bottom flask was charged with 2-(4-((2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)-2-methylpropanoic acid (0.33 g, ˜0.40 mmol) in dichloromethane (10 ml). To this mixture at 0° C. was added oxalyl chloride (0.17 mL, 2.00 mmol) followed by DMF (1 drop). After stirring for 3 h, the volatile material was removed under reduced pressure to afford crude acid chloride. The residue was dissolved in dichloromethane (20 mL), cooled to 0° C. and 7N ammonia in methanol (14.0 mL, 98 mmol) was added. After stirring for 1.25 h the volatile material was removed under reduced pressure. The residue was absorbed onto silica (5 g). Purification by chromatography on silica using hexanes/ethyl acetate as eluent afforded 2-(4-((2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)-2-methylpropanamide (0.128 g, 79%) as a white solid. MW=404.93. 1H NMR (CDCl3, 500 MHz) δ 7.92-7.90 (m, 1H), 7.80-7.77 (m, 1H), 7.37-7.31 (m, 4H), 7.24 (s, 1H), 7.16 (d, J=8.5 Hz, 2H), 5.32 (br s, 1H), 5.16 (br s, 1H), 3.96 (s, 2H), 3.09 (t, J=7.5 Hz, 2H), 2.88 (t, J=7.5 Hz, 2H), 2.15 (quin, J=7.5 Hz, 2H), 1.57 (s, 6H). Treatment with 1.25M HCl in methanol (0.72 mL, 0.90 mmol) afforded the title compound (0.124 g, 94%) as a white solid. MW=441.39. M.p. 180-182° C. 1H NMR (DMSO-d6, 500 MHz) δ 8.10-8.07 (m, 1H), 7.99-7.94 (m, 1H), 7.88 (br s, 1H), 7.58-7.52 (m, 2H), 7.29-7.22 (m, 4H), 6.83 (s, 2H), 5.50 (br s, 1H), 4.03 (s, 2H), 3.06 (t, J=7.5 Hz, 2H), 2.92 (t, J=7.5 Hz, 2H), 2.11 (quin, J=7.5 Hz, 2H), 1.39 (s, 6H); APCI MS m/z 405 [M+H]+.

Workup

  1. customthe volatile material was removed under reduced pressure
  2. customto afford crude acid chloride
  3. stirringAfter stirring for 1.25 h the volatile material
  4. customwas removed under reduced pressure
  5. customThe residue was absorbed onto silica (5 g)
  6. customPurification by chromatography on silica

Sources & evidence

ORD record
ord-51cf37615c7e471a92f93fa46c75bf8e
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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