Methanol → Cis(+/-)6-[({1-[2-(5,7-difluoro-2-oxoquinolin-1(2H)-yl)ethyl]-3-methoxypiperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 255332Notes

Reaction equation

HRID 255332 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[C:15]([F:21])[CH:16]=[C:17]([F:20])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:22])[CH2:4][C@H:3]1[O:23][CH3:24].[O:25]=[C:26]1[CH2:31][O:30][C:29]2[CH:32]=[CH:33][C:34]([CH:36]=O)=[N:35][C:28]=2[NH:27]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>ClCCl>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[C:19]2[C:14]=1[CH:13]=[CH:12][C:11](=[O:22])[N:10]2[CH2:9][CH2:8][N:5]1[CH2:6][CH2:7][C@H:2]([NH:1][CH2:36][C:34]2[CH:33]=[CH:32][C:29]3[O:30][CH2:31][C:26](=[O:25])[NH:27][C:28]=3[N:35]=2)[C@H:3]([O:23][CH3:24])[CH2:4]1

Participants

6

Reactant 4

HCID 887MethanolHCID 5049666Sodium triacetoxyborohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 69324517Cis(+/-)1-[2-(4-amino-3-methoxypiperidin-1-yl)ethyl]-5,7-difluoroquinolin-2(1H)-one2×

Product 1

HCID 86642650Cis(+/-)6-[({1-[2-(5,7-difluoro-2-oxoquinolin-1(2H)-yl)ethyl]-3-methoxypiperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-oneYield 57.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cis(±)1-[2-(4-amino-3-methoxypiperidin-1-yl)ethyl]-5,7-difluoroquinolin-2(1H)-one (Intermediate 167, 140 mg, 0.42 mmol), 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (WO 2004/058144) (75 mg, 0.42 mmol) and sodium triacetoxy borohydride (250 mg, 1.20 mmol) were reacted as described according to Example 69. Chromatography on silica gel with 5% methanol in dichloromethane containing 0.50% ammonium hydroxide gave 120 mg (57%) of the free base of the product.

Sources & evidence

ORD record
ord-dd03b5e47c0f4b6f92d80e701423b0b4
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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