Triethylamine → N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine

HRID 1063270Notes

Reaction equation

HRID 1063270 reaction equation
[CH2:1]([C:3]1[C:4]([NH:11][C@H:12]2[C@@H:16]([O:17][CH2:18][CH3:19])[CH2:15][N:14](C(OCC3C=CC=CC=3)=O)[CH2:13]2)=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2].C(N(CC)CC)C.C([SiH](CC)CC)C>C(Cl)Cl.[Pd](Cl)Cl>[CH2:18]([O:17][C@H:16]1[CH2:15][NH:14][CH2:13][C@H:12]1[NH:11][C:4]1[C:3]([CH2:1][CH3:2])=[N:8][CH:7]=[C:6]([CH2:9][CH3:10])[N:5]=1)[CH3:19]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 12052Triethylsilane2×HCID 60044802benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate

Product 1

HCID 69689234N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amineYield 91%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate (14.55 g, 36.5 mmole) in CH2Cl2 (0.1 M, 365 ml) under N2 was added palladium chloride (1.29 g, 7.24 mmole) and triethyl amine (7.61 mL, 1.5 eq.). Triethylsilane (8.74 mL, 1.5 eq.) was added dropwise over 15 min. After one hour, an additional 8.74 mL of triethylsilane were added dropwise. After 2 additional hours, the reaction mixture was filtered through celite. Trifluoroacetic acid (8 mL) was added and the reaction mixture was stirred for 30 minutes, basified to pH 10 with 2 N aqueous NaOH and extracted with CH2Cl2 (3×300 ml), dried with MgSO4, filtered and concentrated. Vacuum chromatography was run on a 1 L frit funnel with 5-15% MeOH/CH2Cl2 with 0.5% NH4OH gave 8.75 g (91%) of N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine as an oil. IR (liq.) 3438, 2971, 2935, 2874, 2452, 1580, 1546, 1498, 1465, 1448, 1395, 1343, 1164, 1124, 1078 cm−1 HRMS (ESI) calcd for C14H24N4O+H1 265.2028. found 265.2026. [α]25D=−45° (c 1.02, chloroform).

Workup

  1. filtrationAfter 2 additional hours, the reaction mixture was filtered through celite
  2. additionTrifluoroacetic acid (8 mL) was added
  3. extractionextracted with CH2Cl2 (3×300 ml)
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customVacuum chromatography was run on a 1 L frit funnel with 5-15% MeOH/CH2Cl2 with 0.5% NH4OH

Sources & evidence

ORD record
ord-9f665dc2028e41e0b2325bc11fa6387a
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

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