Hydrochloric Acid → HCID 67229109, compound

HRID 1844307Notes

Reaction equation

HRID 1844307 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 (3x). 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 (3x)
  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-25cc80f306214baa8ce61f061811591a
Source dataset
uspto-grants-2015_02
Patent number
US08946413B2

Reaction notes

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