Diisopropylethylamine → N-methyl-2-((R)-3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)-N-((R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide

HRID 1444732Notes

Reaction equation

HRID 1444732 reaction equation
[O:1]=[C:2]1[NH:7][CH:6]=[CH:5][N:4]([S:8]([C:11]2[CH:17]=[CH:16][C:14]([CH3:15])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[C@@H:3]1[CH2:18][C:19]([OH:21])=O.C1CN(C(Cl)=[N+]2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH3:41][NH:42][C@H:43]1[C:52]2[C:47](=[CH:48][C:49]([CH2:53][N:54]3[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]3)=[CH:50][CH:51]=2)[CH2:46][CH2:45][CH2:44]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:41][N:42]([C@H:43]1[C:52]2[C:47](=[CH:48][C:49]([CH2:53][N:54]3[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]3)=[CH:50][CH:51]=2)[CH2:46][CH2:45][CH2:44]1)[C:19](=[O:21])[CH2:18][C@@H:3]1[C:2](=[O:1])[NH:7][CH:6]=[CH:5][N:4]1[S:8]([C:11]1[CH:17]=[CH:16][C:14]([CH3:15])=[CH:13][CH:12]=1)(=[O:10])=[O:9]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27366521-(Chloro-1-pyrrolidinylmethylene)pyrrolidinium HexafluorophosphateHCID 59167870(R)-2-(3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)acetic acidHCID 68679772(R)-N-methyl-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-amine

Product 1

HCID 68681617N-methyl-2-((R)-3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)-N-((R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In 10 ml of dry DCM, 0.5 mmol of (R)-2-(3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)acetic acid and 0.5 mmol of PyClU were combined. Next, 0.6 mmol of (R)—N-methyl-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-amine (prepared in Example 11) and 1.5 mmol of DIEA were added and the mix was stirred at room temperature under nitrogen for 1 h. The reaction was then quenched with 20 ml of saturated sodium bicarbonate, then extracted with EtOAc (2×30 ml), washed with brine (1×20 ml), dried with sodium sulfate, and concentrated. Purification by chomatography over silica gel using 0 to 15% MeOH (2M ammonia) in ethyl acetate gave the title compound. MS 551 (ESI, pos. ion). Similarly, N-methyl-2-((R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydropyrazin-2-yl)-N—((R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide, N-methyl-2-((R)-3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)-N—((R)-7-(piperidin-1-ylmethyl)choman-4-yl)acetamide, N-methyl-2-((R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydropyrazin-2-yl)-N—((R)-7-(piperidin-1-ylmethyl)choman-4-yl)acetamide, N—((R)-7-((tert-butylamino)methyl)choman-4-yl)-N-methyl-2-((R)-3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)acetamide, and N—((R)-6-((tert-butylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-N-methyl-2-((R)-3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)acetamide were prepared.

Workup

  1. customThe reaction was then quenched with 20 ml of saturated sodium bicarbonate
  2. extractionextracted with EtOAc (2×30 ml)
  3. washwashed with brine (1×20 ml)
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated
  6. customPurification by chomatography over silica gel using 0 to 15% MeOH (2M ammonia) in ethyl acetate

Sources & evidence

ORD record
ord-c5e34410fc2f415a884fa00ce3307a10
Source dataset
uspto-grants-2010_02
Patent number
US07662811B2

Reaction notes

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