Hydrochloric Acid → HCID 67229109, compound

HRID 2067841Notes

Reaction equation

HRID 2067841 reaction equation
Cl.[C@H:2]12[CH2:8][C@H:5]([NH:6][CH2:7]1)[CH2:4][N:3]2[C:9]([C@@:11]1([CH2:25][CH3:26])[CH2:15][CH2:14][C@@H:13]([NH:16][C@@H:17]2[CH2:22][CH2:21][O:20][CH2:19][C@H:18]2[O:23][CH3:24])[CH2:12]1)=[O:10].C(N(CC)CC)C.Cl[C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][N:36]=1>CS(C)=O>[CH2:25]([C@:11]1([C:9]([N:3]2[CH2:4][C@@H:5]3[CH2:8][C@H:2]2[CH2:7][N:6]3[C:35]2[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][N:36]=2)=[O:10])[CH2:15][CH2:14][C@@H:13]([NH:16][C@@H:17]2[C@H:18]([O:23][CH3:24])[CH2:19][O:20][CH2:21][CH2:22]2)[CH2:12]1)[CH3:26]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 1449582-Chloro-4-(trifluoromethyl)pyridineHCID 67229296HCID 67229296, compound

Product 1

HCID 67229109HCID 67229109, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of HCl salt of (1S,4S)-2,5-diaza-bicyclo[2.2.1]heptan-2-yl((1S,3R)-1-ethyl-3-((3S,4R)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)methanone (118 mg, 0.33 mmol) in DMSO (2 ml) was added triethylamine (0.15 ml, 1.08 mmol) and the 2-chloro-4-(trifluoromethyl)pyridine (183 mg, 1.01 mmol). The reaction was heated to 120° C. for 15 hours. The reaction was cooled to room temperature, and added to stirring ice water. The mixture was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over MgSO4 concentrated under reduced pressure and purified with the Biotage (0-100% methanol/ethyl acetate, 15 column volumes) to give the product as a brown foam (40 mg 26%). LC/MS (M+H)=497.2739 exp, 497.2884 obs; 1H NMR (400 MHz, CDCl3) δ ppm 8.25-8.24 (1H), 6.75-6.74 (1H), 6.51-6.45 (1H), 5.13-4.76 (2H), 4.10-4.03 (1H), 3.95-3.90 (1H), 3.72-3.16 (11H), 2.82-2.67 (1H), 2.58-2.36 (1H), 2.06-1.36 (12H), 0.86-0.67 (3H)

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. additionadded
  3. extractionThe mixture was extracted with ethyl acetate (3×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. custompurified with the Biotage (0-100% methanol/ethyl acetate, 15 column volumes)

Sources & evidence

ORD record
ord-508c734081ba4da0b693e086a623caf2
Source dataset
uspto-grants-2012_10
Patent number
US08293903B2

Reaction notes

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