Acryloyl chloride → evobrutinib

HRID 1522292Notes

Reaction equation

HRID 1522292 reaction equation
Cl[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[N:6][C:7]=1Cl.[NH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20]C(C)(C)C)=O)[CH2:14][CH2:13]1.[O:25]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[C:41](Cl)(=O)[CH:42]=C>>[NH2:9][C:3]1[N:4]=[CH:5][N:6]=[C:7]([NH:10][CH2:11][CH:12]2[CH2:13][CH2:14][N:15]([C:18](=[O:20])[CH:41]=[CH2:42])[CH2:16][CH2:17]2)[C:2]=1[C:29]1[CH:30]=[CH:31][C:26]([O:25][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:27][CH:28]=1

Participants

5

Reactant 4

HCID 13140Acryloyl chlorideHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 27343774-Phenoxyphenylboronic acidHCID 242192625,6-Dichloro-pyrimidin-4-ylamine

Product 1

HCID 71479709evobrutinib

Procedure

1-(4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)piperidin-1-yl)prop-2-en-1-one was prepared from 5,6-dichloropyrimidin-4-amine, tert-butyl 4-(aminomethyl)piperidine-1-carboxylate, (4-phenoxyphenyl)boronic acid and acryloyl chloride in four steps according to Scheme 2 (using Method B/I, Method C, Method D, and Method F). HPLC purity 97%, RT=3.665 min; MS: m/z=430 [M+H]+, RT=1.53 min. 1H-NMR (DMSO-d6) δ 7.93 (s, 1H), 7.40 (t, 2H), 7.21-7.08 (m, 8H), 6.76 (dd, 1H), 6.04 (d, 1H), 5.61 (d, 1H), 5.43 (s, 2H), 4.34 (d, 1H), 3.98 (d, 1H), 3.12 (t, 2H), 2.95 (t, 1H), 2.56 (t, 1H), 1.81 (m, 1H), 1.59 (m, 2H), 0.92 (m, 2H).

Sources & evidence

ORD record
ord-8b62a59418f644499df579b9d6f3ebf3
Source dataset
uspto-grants-2015_07
Patent number
US09073947B2

Reaction notes

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