Dimethylformamide → 2-[(1R)-8-[(4-[methyl[2-(pyridin-2-yl)ethyl]amino]cyclohexyl)oxy]-1H,2H,3H,4H-cyclopenta[alpha]inden-1-yl]acetamide

HRID 1503995Notes

Reaction equation

HRID 1503995 reaction equation
Cl.[CH3:2][NH:3][CH:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[C:22]3[C:21]4[C@@H:20]([CH2:23][C:24]([NH2:26])=[O:25])[CH2:19][CH2:18][C:17]=4S[C:15]=3N=CN=2)[CH2:6][CH2:5]1.CCN(C(C)C)[CH:30]([CH3:32])[CH3:31].Br[CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1.[CH3:45]N(C=O)C>O>[CH3:2][N:3]([CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH:4]1[CH2:5][CH2:6][CH:7]([O:10][C:11]2[C:22]3[C:21]([CH2:32][CH:30]=[CH:31][CH:15]=3)=[C:17]3[CH2:18][CH2:19][C@H:20]([CH2:23][C:24]([NH2:26])=[O:25])[C:45]=23)[CH2:8][CH2:9]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 129138582-(2-Bromoethyl)pyridineHCID 86695149HCID 86695149, compound

Product 1

HCID 1214540992-[(1R)-8-[(4-[methyl[2-(pyridin-2-yl)ethyl]amino]cyclohexyl)oxy]-1H,2H,3H,4H-cyclopenta[alpha]inden-1-yl]acetamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

The hydrochloride (111 mg, 0.29 mmol, 1.00 equiv) in 4 mL of distilled DMF was added DIEA (119 mg, 0.92 mmol, 3.13 equiv) and 2-(2-bromoethyl)pyridine (57 mg, 0.31 mmol, 1.04 equiv) at room temperature. The resulting solution was stirred overnight at 100° C. in an oil bath. The resulting mixture was diluted with water and extracted with DCM and concentrated under vacuum. The crude product (110 mg) was purified by preparative HPLC under the following conditions (Waters): column: Xbridge Prep C18, 5 um, 19*50 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 25% in 10 min, up to 95% in 1.5 min, down to 10% in 1.5 min); UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated under reduced pressure to remove CH3CN and water. The residue was lyophilized overnight to give the desired 2-[(1R)-8-[(4-[methyl[2-(pyridin-2-yl)ethyl]amino]cyclohexyl)oxy]-1H,2H,3H,4H-cyclopenta[α]inden-1-yl]acetamide (16.3 mg) as a light yellow solid. MS: m/z 466 (M+H)+. 1H NMR (400 MHz, CD3OD): δ 8.48 (d, 2H), 7.80 (t, 1H), 7.79 (d, 1H), 7.77-7.27 (m, 1H), 5.29-5.23 (m, 1H), 3.81-3.79 (m, 1H), 3.16-3.10 (m, 1H), 3.03-2.93 (m, 6H), 2.78-2.73 (m, 2H), 2.44 (s, 3H), 2.33-2.26 (m, 4H), 2.02 (d, 3H), 1.68-1.59 (m, 4H), 1.57-1.54 (m, 1H).

Workup

  1. extractionextracted with DCM
  2. concentrationconcentrated under vacuum
  3. customThe crude product (110 mg) was purified by preparative HPLC under the following conditions (Waters)
  4. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 25% in 10 min
  5. waitup to 95% in 1.5 min
  6. waitdown to 10% in 1.5 min)
  7. customThe product-containing fractions were collected
  8. custompartially evaporated under reduced pressure
  9. customto remove CH3CN and water
  10. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-c05eacb99fe24f39aacce57a3f40ce73
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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