Pyridine → HCID 86648186, compound

HRID 2191376Notes

Reaction equation

HRID 2191376 reaction equation
[Cl:1][C:2]1[C:3]([NH:8][CH2:9][C:10]([C@H:12]2[C@H:19]3[C@H:15]([O:16][C:17]([CH3:21])([CH3:20])[O:18]3)[C:14]([CH2:22][O:23][C:24]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:13]2)=O)=[N:4][CH:5]=[CH:6][N:7]=1.N1C=CC=CC=1.C(O)(C(F)(F)F)=O.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([C@H:12]3[C@H:19]4[C@H:15]([O:16][C:17]([CH3:20])([CH3:21])[O:18]4)[C:14]([CH2:22][O:23][C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[CH:13]3)=[CH:9][N:8]=2)[CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 9845Trifluoroacetic anhydrideHCID 73553419HCID 73553419, compound

Product 1

HCID 86648186HCID 86648186, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-(3-chloropyrazin-2-ylamino)-1-((3aS,4R,6aR)-2,2-dimethyl-6-(trityloxymethyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)ethanone (1-7) (401 mg, 0.69 mmol, 1 equiv) was dissolved in toluene (5.1 mL) and cooled to 0° C. Pyridine (0.67 mL, 8.27 mmol, 12 equiv) was added followed by TFA (0.37 mL, 4.82 mmol, 7 equiv). After 30 minutes, TFAA (0.68 mL, 4.82 mmol, 7 equiv) was added. The resulting mixture was allowed to warm to 15° C. and stirred for 20 h. The reaction was diluted with toluene, washed with sodium bicarbonate, dried (MgSO4), and concentrated. The yellow residue was purified via flash chromatography on silica gel column (ethyl acetate/hexanes) to yield of 8-chloro-3-((3aS,4S,6aR)-2,2-dimethyl-6-(trityloxymethyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)imidazo[1,2-a]pyrazine (1-8) as an off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.93 (d, 1H, J=3 Hz), 7.64 (d, 1H, J=3 Hz), 7.21-7.49 (m, 15H), 5.94 (br s, 2H), 5.06 (d, 1H, J=5.5 Hz), 4.98 (d, 1H, J=5.5 Hz), 4.45 (m, 2H), 3.89 (d, 1H, J=14.5 Hz), 3.76 (m, 1H), 3.71 (d, 1H, J=14.5 Hz), 1.36 (s, 3H), 1.33 (s, 3H). LRMS m/z (M+H) 563.9 found, 564.2 required.

Workup

  1. temperatureto warm to 15° C.
  2. washwashed with sodium bicarbonate
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe yellow residue was purified via flash chromatography on silica gel column (ethyl acetate/hexanes) to yield of 8-chloro-3-((3aS,4S,6aR)-2,2-dimethyl-6-(trityloxymethyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)imidazo[1,2-a]pyrazine (1-8) as an off-white solid

Sources & evidence

ORD record
ord-461d2cccdcbd4185b7be853fc7fe43a2
Source dataset
uspto-grants-2012_12
Patent number
US08329697B2

Reaction notes

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