Water → N-{2-[(2-fluoropyridin-3-yl)amino]-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl}acetamide
Reaction equation
[F:1][C:2]1[C:7]([NH:8][C:9]([NH2:11])=[S:10])=[CH:6][CH:5]=[CH:4][N:3]=1.Br.Br[CH2:14][C:15]([C:17]1[S:21][C:20]([NH:22][C:23](=[O:25])[CH3:24])=[N:19][C:18]=1[CH3:26])=O.O>CCO>[F:1][C:2]1[C:7]([NH:8][C:9]2[S:10][CH:14]=[C:15]([C:17]3[S:21][C:20]([NH:22][C:23](=[O:25])[CH3:24])=[N:19][C:18]=3[CH3:26])[N:11]=2)=[CH:6][CH:5]=[CH:4][N:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
According to the general procedure 1, N-(2-fluoropyridin-3-yl)thiourea (prepared from 3-amino-2-fluoropyridine (Asymchem), following procedure D) is added to a solution of N-[5-(bromoacetyl)-4-methyl-1,3-thiazol-2-yl]acetamide, hydrobromide salt (Intermediate 1) and TEA (3 eq) in EtOH. The mixture is stirred for 2 h at RT. After addition of water, the desired product is filtrated off and washed with water. N-{2-[(2-fluoropyridin-3-yl)amino]-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl}acetamide is isolated as a pale yellow solid (57%). The hydrochloride salt of a batch of N-{2-[(2-fluoropyridin-3-yl)amino]-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl}acetamide (200.00 mg; 0.57 mmol; 1.00 eq.) is prepared. It is suspended in MeOH (10.00 ml) and hydrogen chloride (2.29 ml; 1.25 M; 2.86 mmol; 5.00 eq.) in methanol is added. The mixture is stirred during 20 minutes at RT and filtered. The yellow powder obtained is washed with diethyl ether and dried under vacuo, affording compound (43) in 79% yield. 1H NMR (DMSO-d6, 300 MHz) δ 2.13 (s, 3H), 2.47 (s, 3H), 3.15 (s, 2H), 7.01 (s, 1H), 7.36 (m, 1H), 7.77 (m, 1H), 8.94 (m, 1H), 10.39 (s, 1H), 12.07 (s, 1H). M− (ESI): 347.8; M+ (ESI): 349.8. HPLC, Rt: 3.0 min (purity: 100%).
Workup
- filtrationthe desired product is filtrated off
- washwashed with water
Sources & evidence
- ORD record
- ord-aefa78758d7b4fcba3ae4015176ef8f6
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08802861B2
Reaction notes
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