Cyanoacetic acid → HCID 118114844, compound

HRID 1050615Notes

Reaction equation

HRID 1050615 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[N:16]=[C:17]([N:24]4[CH2:29][CH2:28][CH2:27][C@@H:26]([NH:30][C:31]([N:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)=[O:32])[CH2:25]4)[N:18]=[N:19][C:20]=3[C:21]([NH2:23])=[O:22])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[C:39]([CH2:41][C:42](O)=[O:43])#[N: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>CN(C=O)C>[C:39]([CH2:41][C:42]([N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[N:16]=[C:17]([N:24]4[CH2:29][CH2:28][CH2:27][C@@H:26]([NH:30][C:31]([N:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)=[O:32])[CH2:25]4)[N:18]=[N:19][C:20]=3[C:21]([NH2:23])=[O:22])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1)=[O:43])#[N:40]

Participants

6

Reactant 4

HCID 9740Cyanoacetic acidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 118115365HCID 118115365, compound

Product 1

HCID 118114844HCID 118114844, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-5-(4-(Piperidin-4-yl)phenylamino)-3-(3-(piperidine-1-carboxamido)piperidin-1-yl)-1,2,4-triazine-6-carboxamide hydrochloride (494) (75 mg, 0.14 mmol) was dissolved in 4 mL DMF. To it were added 2-cyanoacetic acid (36 mg, 0.42 mmol), DIEA (250 μL, 1.40 mmol) and then PyBOP (150 mg, 0.28 mmol). The mixture was stirred at RT for 45 min, quenched with 0.3 mL TFA, and directly subjected to reverse phase prep HPLC to isolate the title compound, (R)-5-(4-(1-(2-cyanoacetyl)piperidin-4-yl)phenylamino)-3-(3-(piperidine-1-carboxamido)piperidin-1-yl)-1,2,4-triazine-6-carboxamide (500), as HCl salt (76 mg). LC-MS (ESI): m/z (M+1) 575.3. UV: λ=262, 329, 337 nm.

Workup

  1. customquenched with 0.3 mL TFA

Sources & evidence

ORD record
ord-e049b2ebedce4027964b505b10fca9cf
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

Loading…