Diisopropylethylamine → 6-[({1-[2-(7-Methoxy-2-oxo-2H-3,1-benzoxazin-1(4H)-yl)ethyl]piperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 255270Notes

Reaction equation

HRID 255270 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:22]3[CH:23]=[C:24]([O:27][CH3:28])[CH:25]=[CH:26][C:21]=3[CH2:20][O:19][C:18]2=[O:29])[CH2:11][CH2:10]1.C(N(CC)C(C)C)(C)C.[O:39]=[C:40]1[CH2:45][O:44][C:43]2[CH:46]=[CH:47][C:48]([CH:50]=O)=[N:49][C:42]=2[NH:41]1.C([BH3-])#N.[Na+]>>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]2[CH2:20][O:19][C:18](=[O:29])[N:17]([CH2:16][CH2:15][N:12]3[CH2:11][CH2:10][CH:9]([NH:8][CH2:50][C:48]4[CH:47]=[CH:46][C:43]5[O:44][CH2:45][C:40](=[O:39])[NH:41][C:42]=5[N:49]=4)[CH2:14][CH2:13]3)[C:22]=2[CH:23]=1

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 667737611-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxy-1,4-dihydro-2H-3,1-benzoxazin-2-one trifluoro acetate2×

Product 1

HCID 159821516-[({1-[2-(7-Methoxy-2-oxo-2H-3,1-benzoxazin-1(4H)-yl)ethyl]piperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

Procedure

1-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxy-1,4-dihydro-2H-3,1-benzoxazin-2-one trifluoro acetate (Intermediate 106) (324 mg, 0.78 mmol) was converted to the free base using N,N-diisopropylethylamine for 30 minutes and reacted with 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (WO 2004/058144) (153 mg, 0.86 mmol) and sodium cyanoborohydride (98 mg, 1.56 mmol) as described under Example 21. The reaction mixture was filtered through a 0.45 μm membrane and concentrated to dryness under reduced pressure. Chromatography on silica gel with dichloromethane/methanol (9:1) gave the free base of the title compound as a colorless foam. The free base was taken up in 1,4 dioxane (2 mL), followed by addition of 4M HCl in 1,4-dioxane (0.30 mL). The resulting precipitate was collected by filtration and gave 75 mg (48%) of the bis-hydrochloride salt of the product.

Workup

  1. customfor 30 minutes
  2. filtrationThe reaction mixture was filtered through a 0.45 μm membrane
  3. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-68ac0880321d413cada3662c57afb8e5
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

Loading…