Diisopropylethylamine → Hydrochloric Acid

HRID 1050519Notes

Reaction equation

HRID 1050519 reaction equation
[ClH:1].[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.[CH3:34][N:35]([CH3:42])[CH2:36]/[CH:37]=[CH:38]/[C:39](O)=[O:40].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN1C(=O)CCC1>[CH3:34][N:35]([CH3:42])[CH2:36]/[CH:37]=[CH:38]/[C:39]([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:40].[ClH:1]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 14805664(2E)-4-(Dimethylamino)-2-butenoic acidHCID 118114633(R)-5-(methyl(piperidin-3-yl)amino)-3-(4-(morpholine-4-carbonyl)phenylamino)pyrazine-2-carboxamide hydrochloride

Product 2

HCID 313Hydrochloric AcidYield 946.9%HCID 118114641US9656988, Example 75

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 (E)-4-(dimethylamino)but-2-enoic acid (42 mg, 0.25 mmol), DIEA (150 μL, 0.84 mmol) and then PyBOP (88 mg, 0.17 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 (94) as an HCl salt (29 mg). MS found for C28H38N8O4 as (M+H)+ 551.3, (M−H)− 549.3. UV: λ=274, 281, 313, 344, 369 nm.

Workup

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

Sources & evidence

ORD record
ord-8cef7419087a4dd8acbc38b3ab2fc975
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

Loading…