Diisopropylethylamine → 7-Chloro-1-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]piperidin-1-yl}ethyl)-1,8-naphthyridin-2(1H)-one

HRID 1644425Notes

Reaction equation

HRID 1644425 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([Cl:27])[N:25]=3)[CH:20]=[CH:19][C:18]2=[O:28])[CH2:11][CH2:10]1.C(N(C(C)C)CC)(C)C.[O:38]1[C:47]2[CH:46]=[C:45]([CH:48]=O)[N:44]=[CH:43][C:42]=2[O:41][CH2:40][CH2:39]1.C([BH3-])#N.[Na+]>ClCCl.C(#N)C.O.CO>[Cl:27][C:24]1[N:25]=[C:26]2[C:21]([CH:20]=[CH:19][C:18](=[O:28])[N:17]2[CH2:16][CH2:15][N:12]2[CH2:11][CH2:10][CH:9]([NH:8][CH2:48][C:45]3[N:44]=[CH:43][C:42]4[O:41][CH2:40][CH2:39][O:38][C:47]=4[CH:46]=3)[CH2:14][CH2:13]2)=[CH:22][CH:23]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 866426401-[2-(4-Aminopiperidin-1-yl)ethyl]-7-chloro-1,8-naphthyridin-2(1H)-one trifluoroacetate2×

Product 1

HCID 159824067-Chloro-1-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]piperidin-1-yl}ethyl)-1,8-naphthyridin-2(1H)-oneYield 11.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

1-[2-(4-Aminopiperidin-1-yl)ethyl]-7-chloro-1,8-naphthyridin-2(1H)-one trifluoroacetate (Intermediate 138, crude, 405 mg, 0.76 mmol), di-isopropyl ethylamine (0.38 mL, 2.27 mmol), 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde [WO 2004/058144](180 mg, 1.1 mmol) and sodium cyanoborohydride (100 mg, 1.56 mmol) were reacted as described for Example 21. Chromatography on silica gel using methanol in dichloromethane (0-20% with 1% aqueous ammonium hydroxide) followed by reverse phase chromatography with 20-75% acetonitrile/water/10 mM NH4OAc Buffer) gave the title compound (39 mg, 11%).

Sources & evidence

ORD record
ord-9393890962c34e6bbba016855e82bea7
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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