Potassium Carbonate → 2-[(9R)-9-(2-{4H,5H,6H-thieno[2,3-c]pyrrol-5-yl}ethyl)-6-oxaspiro[4.5]decan-9-yl]pyridine
Reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C@@:7]1([CH2:17][CH2:18][NH2:19])[CH2:16][C:11]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[O:10][CH2:9][CH2:8]1.C(NCC[C@]1(C2C=CC(F)=CC=2)CC2(CCCC2)OCC1)C1C=CC=CC=1.Br[CH2:48][C:49]1[S:50][CH:51]=[CH:52][C:53]=1[CH2:54]Br.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[S:50]1[C:49]2[CH2:48][N:19]([CH2:18][CH2:17][C@:7]3([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)[CH2:16][C:11]4([CH2:15][CH2:14][CH2:13][CH2:12]4)[O:10][CH2:9][CH2:8]3)[CH2:54][C:53]=2[CH:52]=[CH:51]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of 2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethan-1-amine (0.030 g, 0.115 mmol; prepared by following a sequence described for Compound 81 in dried ACN (5.8 mL) was added 2,3-bis(bromomethyl)thiophene (31.1 mg, 0.115 mmol) followed by addition of K2CO3 (79.62 mg, 0.576 mmol). After 30 min, LCMS showed that the reaction was done and the major peak had the corresponding mass to the desired product. It was then subjected to HPLC purification. HPLC purification method: Luna acid medium column, 10-50% acetonitrile in H2O over 15 min, followed by flashing with 100% acetonitrile, 0.1% TFA modifier was employed. The fractions containing the desired product were pooled, basified with 2N NaOH and extracted with DCM (3×20 mL). The combined organics were concentrated and purified with flash chromatography (10 g silica gel column, eluted by 0-10% MeOH in DCM, based upon TLC measurement: DCM/MeOH (10/1) Rf=0.60) to afford 5 mg of 2-[(9R)-9-(2-{4H,5H,6H-thieno[2, 3-c]pyrrol-5-yl}ethyl)-6-oxaspiro[4.5]decan-9-yl]pyridine as a colorless oil in 12% yield.
Workup
- customprepared
Sources & evidence
- ORD record
- ord-51587054da0f45b79e494b4450d3b799
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08835488B2
Reaction notes
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