Isopropanol → 6'-(3-Fluoropropoxy)-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thione

HRID 539333Notes

Reaction equation

HRID 539333 reaction equation
[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11]3([CH2:20][CH2:19][CH:18]([O:21][CH3:22])[CH2:17][CH2:16]3)[C:12]2=[NH:15])=[CH:8][CH:7]=1.C(OC)(OC)OC.CC(O)C.O=[C:35]([CH3:39])[C:36](=[S:38])[NH2:37]>CO.CCCCCCC.CCOC(C)=O>[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11]3([C:12]42[NH:37][C:36](=[S:38])[C:35]([CH3:39])=[N:15]4)[CH2:16][CH2:17][CH:18]([O:21][CH3:22])[CH2:19][CH2:20]3)=[CH:8][CH:7]=1

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 9005Trimethyl orthoformateHCID 207652372-Oxopropanethioamide2×HCID 679795506'-(3-Fluoropropoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine

Product 1

HCID 866672726'-(3-Fluoropropoxy)-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thioneYield 64%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Conditions

Temperature
60 °C

Procedure

6′-(3-Fluoropropoxy)-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-imine (Example 20v, Step 2, 204 mg, 0.67 mmol), trimethyl orthoformate (0.193 mL, 1.76 mmol) and 2-propanol (5 mL) was added to a MW vial. The vial was sealed and the mixture was heated at 60° C. (oil bath). 2-Oxopropanethioamide (Intermediate 2, 138 mg, 1.34 mmol) in MeOH (15 mL) was added and the resulting mixture was stirred overnight at 60° C. and was then concentrated in vacuo. The product was isolated using flash chromatography (0-50% EtOAc in heptane) to give the title compound (167 mg, 64% yield): MS (ES+) m/z 391 [M+H]+.

Workup

  1. customThe vial was sealed
  2. concentrationwas then concentrated in vacuo
  3. customThe product was isolated

Sources & evidence

ORD record
ord-5eb8b115f05e4108904db4c6a3f26e1a
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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