2-Butynoic acid → HCID 118114692, compound

HRID 1050617Notes

Reaction equation

HRID 1050617 reaction equation
[N:1]1([C:7]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[N:17]=[C:18]([NH:25][C@@H:26]4[CH2:30][CH2:29][NH:28][CH2:27]4)[N:19]=[N:20][C:21]=3[C:22]([NH2:24])=[O:23])=[CH:11][CH:10]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:31](O)(=[O:35])[C:32]#[C:33][CH3:34].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>[C:31]([N:28]1[CH2:29][CH2:30][C@@H:26]([NH:25][C:18]2[N:19]=[N:20][C:21]([C:22]([NH2:24])=[O:23])=[C:16]([NH:15][C:12]3[CH:13]=[CH:14][C:9]([C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[O:8])=[CH:10][CH:11]=3)[N:17]=2)[CH2:27]1)(=[O:35])[C:32]#[C:33][CH3:34]

Participants

6

Reactant 4

HCID 685352-Butynoic acidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 118114933HCID 118114933, compound

Product 1

HCID 118114692HCID 118114692, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of (R)-5-(4-(morpholine-4-carbonyl)phenylamino)-3-(pyrrolidin-3-ylamino)-1,2,4-triazine-6-carboxamide (83) (90 mg, 0.22 mmol) in NMP (4 mL) were 2-butynoic acid (55 mg, 0.66 mmol), DIEA (380 μL, 2.2 mmol) and then PyBOP (230 mg, 0.44 mmol). The mixture was stirred at RT for 30 min, quenched with TFA (0.6 mL), diluted with 2 mL water, and subjected to reverse phase preparative HPLC using 0.1% formic acid in water and neat MeCN to isolate the title compound, (R)-3-(1-but-2-ynoylpyrrolidin-3-ylamino)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide (505) as formic acid salt. LC-MS (ESI): m/z (M+1) 479.1. UV: λ=280 nm. Proton NMR (CD3OD): δ 7.87 (2H, m), 7.47 (2H, m), 4.56 (1H, m), 4.07 (1H, m), 3.88-3.77 (2H, m), 3.75-3.44 (9H, m), 2.37 (1H, m), 2.15 (1H, m), 2.05 (3H, s) ppm.

Workup

  1. customquenched with TFA (0.6 mL)
  2. additiondiluted with 2 mL water

Sources & evidence

ORD record
ord-38b822b73e194311bb81637519f54ca0
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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