Hydrochloric Acid → HCID 67229334, compound

HRID 2067849Notes

Reaction equation

HRID 2067849 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=1.Cl.[C@H:13]12[CH2:19][C@H:16]([NH:17][CH2:18]1)[CH2:15][N:14]2[C:20]([C@@:22]1([CH2:36][CH:37]([F:39])[F:38])[CH2:26][CH2:25][C@@H:24]([NH:27][C@@H:28]2[C@H:33]([O:34][CH3:35])[CH2:32][O:31][CH2:30][CH2:29]2)[CH2:23]1)=[O:21].C(N(CC)CC)C>CS(C)=O>[F:39][CH:37]([F:38])[CH2:36][C@:22]1([C:20]([N:14]2[CH2:15][C@@H:16]3[CH2:19][C@H:13]2[CH2:18][N:17]3[C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=2)=[O:21])[CH2:26][CH2:25][C@@H:24]([NH:27][C@@H:28]2[C@H:33]([O:34][CH3:35])[CH2:32][O:31][CH2:30][CH2:29]2)[CH2:23]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 6023342-Chloro-6-(trifluoromethyl)pyridine2×HCID 67228981HCID 67228981, compound

Product 1

HCID 67229334HCID 67229334, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

Prepared as described in example 24 using 2-chloro-6-(trifluoromethyl)pyridine in place of 4-chloro-6-(trifluoromethyl)pyrimidine and modifying step 9 as follows. To a solution of HCl salt of 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-{[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-3-(2,2-difluoroethyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol (183 mg, 0.43 mmol) in DMSO (2 ml) was added triethylamine (0.2 ml, 1.43 mmol) and 2-chloro-6-(trifluoromethyl)pyridine (179 mg, 1.05 mmol). The reaction was heated to 120° C. for 14.5 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 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-(2,2-difluoroethyl)-3-({(1S,4S)-5-[6-(trifluoromethyl)pyridin-2-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol as a brown foam (58 mg 28%). LC/MS (M+H)=533.2551 exp, 533.2546 obs; 1H NMR (400 MHz, CDCl3) δ ppm 7.54-7.51 (1H), 6.91-6.89 (1H), 6.51-6.38 (1H), 5.94-5.54 (1H), 5.11-4.70 (2H), 4.06-4.01 (1H), 3.93-3.87 (1H), 3.70-3.53 (2H), 3.51-3.31 (6H), 3.27-3.20 (3H), 2.78-2.61 (1H), 2.53-2.36 (1H), 2.20-1.80 (7H), 1.68-1.38 (5H)

Workup

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

Sources & evidence

ORD record
ord-6fc3c923a0e64fe5841c960d9d319f39
Source dataset
uspto-grants-2012_10
Patent number
US08293903B2

Reaction notes

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