Acryloyl chloride → Hydrochloric Acid

HRID 1050518Notes

Reaction equation

HRID 1050518 reaction equation
Cl.[CH3:2][N:3]([C@@H:28]1[CH2:33][CH2:32][CH2:31][NH:30][CH2:29]1)[C:4]1[N:5]=[C:6]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[O:21])=[CH:16][CH:15]=2)[C:7]([C:10]([NH2:12])=[O:11])=[N:8][CH:9]=1.CCN(C(C)C)C(C)C.[C:43]([Cl:47])(=[O:46])[CH:44]=[CH2:45]>CN1C(=O)CCC1>[C:43]([N:30]1[CH2:31][CH2:32][CH2:33][C@@H:28]([N:3]([CH3:2])[C:4]2[N:5]=[C:6]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)=[O:21])=[CH:16][CH:15]=3)[C:7]([C:10]([NH2:12])=[O:11])=[N:8][CH:9]=2)[CH2:29]1)(=[O:46])[CH:44]=[CH2:45].[ClH:47]

Participants

6

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 118114633(R)-5-(methyl(piperidin-3-yl)amino)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide hydrochloride

Product 2

HCID 313Hydrochloric AcidYield 816.3%HCID 118114761US9656988, Example 74

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of (R)-5-(methyl(piperidin-3-yl)amino)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide hydrochloride (92) (40 mg, 0.084 mmol) in NMP (3 mL) was added DIEA (150 μL, 0.84 mmol) and then acryloyl chloride (23 mg, 0.25 mmol). The mixture was stirred at RT for 1.5 h, quenched with TFA (0.2 mL), diluted with 2 mL water, and subjected to reverse phase preparative HPLC to isolate the title compound (93) as an HCl salt (25 mg). MS found for C25H31N7O4 as (M+H)+ 494.1, (M−H)− 492.3. UV: λ=275, 280, 313, 343, 369 nm.

Workup

  1. customquenched with TFA (0.2 mL)
  2. additiondiluted with 2 mL water

Sources & evidence

ORD record
ord-155c408ca93c4dd399654cb8c652e707
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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