Methanol → 1,1-dimethylethyl {1-[2-(5-chloro-2-oxo-1,3-benzthiazol-3(2H)-yl)ethyl]-4-piperidinyl}(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)carbamate

HRID 657053Notes

Reaction equation

HRID 657053 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8](=[O:10])[N:7]([CH2:11][CH:12]=O)[C:6]=2[CH:14]=1.[O:15]1[C:24]2[CH:23]=[C:22]([CH2:25][N:26]([CH:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[N:21]=[CH:20][C:19]=2[O:18][CH2:17][CH2:16]1.CO>C(Cl)(Cl)Cl.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8](=[O:10])[N:7]([CH2:11][CH2:12][N:37]3[CH2:36][CH2:35][CH:34]([N:26]([CH2:25][C:22]4[N:21]=[CH:20][C:19]5[O:18][CH2:17][CH2:16][O:15][C:24]=5[CH:23]=4)[C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:32])[CH3:30])[CH2:39][CH2:38]3)[C:6]=2[CH:14]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 21487294(5-Chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)acetaldehydeHCID 578154611,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-4-piperidinylcarbamate

Product 1

HCID 866353431,1-dimethylethyl {1-[2-(5-chloro-2-oxo-1,3-benzthiazol-3(2H)-yl)ethyl]-4-piperidinyl}(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)carbamateYield 101.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6212ChloroformSolvent

Procedure

(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)acetaldehyde (0.10 g, 0.44 mmol) and 1,1-dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-4-piperidinylcarbamate (0.154 g, 0.44 mmole) (for a synthesis see WO2004/058144 Example 99(h)) were dissolved in chloroform (10 ml) and MeOH (1.5 ml) and treated with acetic acid (8 drops) and (polystyrylmethyl)trimethylammonium cyanoborohydride (Novabiochem) (4.1 mmol/g, 0.87 g), and the mixture stirred at rt for 60 h. The reaction was filtered and evaporated to dryness. Chromatography on silica gel eluting with a gradient of 0-12% MeOH/DCM gave 1,1-dimethylethyl {1-[2-(5-chloro-2-oxo-1,3-benzthiazol-3(2H)-yl)ethyl]-4-piperidinyl}(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)carbamate as an oil (0.25 g, 100%). MS (ES+) m/z 561 and 563 (MH+). This was dissolved in DCM (10 ml) and treated with trifluoroacetic acid (3 ml) at rt for 18 h then evaporated to dryness. The residue was partitioned between 10% potassium carbonate in water (30 ml) and 10% MeOH in DCM (3×30 ml). The organics were dried, filtered and evaporated to dryness. Chromatography on silica gel eluting with a gradient of 0-10% 2M ammonia in MeOH/DCM gave the free base of the title compound as an oil (0.138 g, 67%).

Workup

  1. filtrationThe reaction was filtered
  2. customevaporated to dryness

Sources & evidence

ORD record
ord-783df43eb7604817bc3d3a899e1c70f5
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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