Phenyl 5-cyanopyrazin-2-ylcarbamate → tert-Butyl 2-(2-chloro-4-(3-(5-cyanopyrazin-2-yl)ureido)phenoxy)ethyl(2,4-difluorobenzyl)carbamate

HRID 1019739Notes

Reaction equation

[NH2:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][CH2:7][CH2:8][N:9]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])[C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[C:4]([Cl:28])[CH:3]=1.[C:29]([C:31]1[N:32]=[CH:33][C:34]([NH:37][C:38](=O)[O:39]C2C=CC=CC=2)=[N:35][CH:36]=1)#[N:30]>CN(C)C=O>[Cl:28][C:4]1[CH:3]=[C:2]([NH:1][C:38]([NH:37][C:34]2[CH:33]=[N:32][C:31]([C:29]#[N:30])=[CH:36][N:35]=2)=[O:39])[CH:27]=[CH:26][C:5]=1[O:6][CH2:7][CH2:8][N:9]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[F:25])[C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:13])[CH3:14]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of tert-butyl 2-(4-amino-2-chlorophenoxy)ethyl(2,4-difluorobenzyl)-carbamate (1.6 g, 3.87 mmol) in N,N-dimethylformamide (4 mL) at RT were phenyl 5-cyanopyrazin-2-ylcarbamate (1.39 g, 5.81 mmol) (Example 10) and N,N,N-diisopropylethylamine (0.751 g, 5.81 mmol) added. The reaction mixture was heated at 60° C. for 1.5 hours then the reaction mixture was poured into ice-water (100 mL) and allowed to stand for 30 minutes. The resulting precipitate was collected, washed with water and air dried. The crude product was purified by column chromatography on neutral silica gel using 0-2% methanol in DCM to give the title compound (0.53 g, 26% yield).

Workup

customat RT
additionadded
customThe resulting precipitate was collected
washwashed with water and air
customdried
customThe crude product was purified by column chromatography on neutral silica gel using 0-2% methanol in DCM

Sources & evidence

ORD record: ord-a9169ecee8d54eac94e7e15b2504a5bc
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716287B2

Reaction notes

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