Sodium Hydroxide → (+/-)-(4-Chloro-2-{2-[2-(2,4-dimethyl-thiazol-5-yl)-cyclopropanecarbonyl]-1,2,3,4-tetrahydro-isoquinolin-1-yl}-phenoxy)-acetic acid

HRID 2036207Notes

Reaction equation

HRID 2036207 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C@@H:8]2[CH2:10][C@H:9]2[C:11]([OH:13])=O)=[C:5]([CH3:7])[N:6]=1.C([O:16][C:17](=[O:37])[CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[CH:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH2:29][NH:28]1)C.Cl.CN(C)CCCN=C=NCC.[OH-].[Na+]>CN(C=O)C.CN(C1C=CN=CC=1)C.C(O)=O>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([O:19][CH2:18][C:17]([OH:37])=[O:16])=[C:21]([CH:27]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:30][CH2:29][N:28]2[C:11]([CH:9]2[CH2:10][CH:8]2[C:4]2[S:3][C:2]([CH3:1])=[N:6][C:5]=2[CH3:7])=[O:13])[CH:22]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66653751(+/-)-[4-Chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl esterHCID 66656330(+/-)-trans-2-(2,4-Dimethyl-thiazol-5-yl)cyclopropanecarboxylic acid

Product 1

HCID 66653993(+/-)-(4-Chloro-2-{2-[2-(2,4-dimethyl-thiazol-5-yl)-cyclopropanecarbonyl]-1,2,3,4-tetrahydro-isoquinolin-1-yl}-phenoxy)-acetic acid

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 284Formic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (±)-trans-2-(2,4-dimethyl-thiazol-5-yl)cyclopropanecarboxylic acid (42 mg, 0.20 mmol, 1.0 eq.) and (±)-[4-chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester (73 mg, 0.20 mmol, 1.0 eq.) in DMF (2.4 mL), DMAP (37 mg, 0.30 mmol, 1.5 eq.) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (58 mg, 0.30 mmol, 1.5 eq.) were added. The resulting solution was stirred at r.t. for 62 hours. 1M aq. NaOH soln. (1.2 mL) was added and the solution was stirred at r.t. for 3.5 hours. Formic acid (0.2 mL) was added. The crude mixture was purified by prep. HPLC (column: Waters XBridge, 19×50 mm, 5 um, UV/MS, acidic conditions). The two racemic diastereoisomers were separated (LC-MS 3: tR (±)-dial=0.81 and tR (±)-dia2=0.82). The title compound showed: tR=0.82.

Workup

  1. addition(1.2 mL) was added
  2. stirringthe solution was stirred at r.t. for 3.5 hours
  3. customThe crude mixture was purified by prep
  4. customThe two racemic diastereoisomers were separated (LC-MS 3

Sources & evidence

ORD record
ord-8a88928ca4d44ca29220cf25f94680c5
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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