Chloroform → HCID 69185047, compound

HRID 656917Notes

Reaction equation

HRID 656917 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:18]4[O:20][CH2:21][CH2:22][O:23][C:17]=4[CH:16]=[CH:15][C:14]=3[CH:13]=[CH:12][C:11]2=[O:24])[CH2:4][CH2:3]1.[O:25]1[C:34]2[CH:33]=[C:32]([CH:35]=O)[N:31]=[CH:30][C:29]=2[O:28][CH2:27][CH2:26]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(Cl)(Cl)[Cl:52]>CO>[ClH:52].[O:25]1[C:34]2[CH:33]=[C:32]([CH2:35][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:18]6[O:20][CH2:21][CH2:22][O:23][C:17]=6[CH:16]=[CH:15][C:14]=5[CH:13]=[CH:12][C:11]4=[O:24])[CH2:6][CH2:7]3)[N:31]=[CH:30][C:29]=2[O:28][CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 5049666Sodium triacetoxyborohydride2×HCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde3×HCID 68993634HCID 68993634, compound

Product 1

HCID 69185047HCID 69185047, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

10-[2-(4-amino-1-piperidinyl)ethyl]-2,3-dihydro[1,4]dioxino[2,3-h]quinolin-9(10H)-one (100 mg; 0.304 mmol) and 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carboxaldehyde (for a synthesis see WO2004058144, Example 2(c) or WO03/087098, Example 19(d)) (50 mg; 0.304 mmol) were dissolved in a 5:1 mixture of chloroform and MeOH (5 ml:1 ml) and stirred at rt for 2.5 h. More 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (10 mg; 0.031 mmol) was added to the reaction and stirred for 20 mins. This was then treated with NaBH(OAc)3 (20 mg; 0.092 mmol) and stirred for 30 mins. More 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (10 mg; 0.031 mmol) was added to the reaction and stirred for 15 mins. This was then treated with NaBH(OAc)3 (20 mg; 0.092 mmol) and stirred for 15 mins. The solvents were then removed and the crude residues purified by column chromatography on silica gel using a 0-20% 2M NH3:MeOH/DCM gradient. Fractions containing the desired were concentrated to afford the free base of the title compound. (140 mg; 96%). δH CDCl3, (400 MHz) 1.49 (m, 2H), 1.8-2.6 (m, 8H), 2.76 (m, 2H), 3.04 (d, 2H), 3.81 (s, 2H), 4.2-4.4 (m, 8H), 4.71 (m, 2H), 6.51 (d, 1H), 6.78 (d, 1H), 6.83 (s, 1H), 7.01 (d, 1H), 7.49 (d, 1H), 8.1 (s, 1H).

Workup

  1. stirringstirred for 20 mins
  2. stirringstirred for 30 mins
  3. stirringstirred for 15 mins
  4. stirringstirred for 15 mins
  5. customThe solvents were then removed
  6. customthe crude residues purified by column chromatography on silica gel using a 0-20% 2M NH3
  7. additionFractions containing the
  8. concentrationdesired were concentrated

Sources & evidence

ORD record
ord-fceac7d806024b6fbf48f628afae637c
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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