Diisopropylethylamine → 4-{3-[4-(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)piperazin-1-yl]propyl}-6-methoxy-2H-1,4-benzoxazin-3(4H)-one

HRID 255286Notes

Reaction equation

HRID 255286 reaction equation
FC(F)(F)[C:3](O)=[O:4].[CH3:8][O:9][C:10]1[CH:29]=[CH:28][C:13]2CO[C:16](=[O:27])[N:17]([CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:12]=2[CH:11]=1.C(N(CC)C(C)C)(C)C.[O:39]1[C:48]2[CH:47]=[C:46]([CH:49]=O)[N:45]=[CH:44][C:43]=2[O:42][CH2:41][CH2:40]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CO>[O:39]1[C:48]2[CH:47]=[C:46]([CH2:49][N:24]3[CH2:23][CH2:22][N:21]([CH2:20][CH2:19][CH2:18][N:17]4[C:12]5[CH:11]=[C:10]([O:9][CH3:8])[CH:29]=[CH:28][C:13]=5[O:4][CH2:3][C:16]4=[O:27])[CH2:26][CH2:25]3)[N:45]=[CH:44][C:43]=2[O:42][CH2:41][CH2:40]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 667736227-Methoxy-1-(3-piperazin-1-ylpropyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one trifluoroacetate2×

Product 1

HCID 159822784-{3-[4-(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)piperazin-1-yl]propyl}-6-methoxy-2H-1,4-benzoxazin-3(4H)-one

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

7-Methoxy-1-(3-piperazin-1-ylpropyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one trifluoroacetate (Intermediate 118, crude, 963 mg, 1.81 mmol) was converted to the free base with N,N-diisopropylethylamine and reacted with 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (WO 2004/058144) (203 mg, 123 mmol) and sodium triacetoxy borohydride (240 mg, 1.10 mmol) as described for Example 55 to give the free base of the product as an oil after chromatography on silica gel with dichloromethane/methanol (93:7), 125 mg (22%).

Sources & evidence

ORD record
ord-e4c9944e71e74a56b5a35e9e123618b8
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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