1-Hydroxybenzotriazole → HCID 73505596, compound

HRID 1508304Notes

Reaction equation

HRID 1508304 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:10]2([C:27]([F:30])([F:29])[F:28])[CH2:14][C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[C:20]3([CH2:26][NH:25][CH2:24]3)[O:19][CH2:18]4)=[N:12][CH2:11]2)[CH:6]=[C:7]([Cl:9])[CH:8]=1.[CH3:31][S:32]([CH2:35][C:36](O)=[O:37])(=[O:34])=[O:33].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[Cl:9][C:7]1[CH:6]=[C:5]([C:10]2([C:27]([F:29])([F:28])[F:30])[CH2:14][C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[C:20]3([CH2:24][N:25]([C:36](=[O:37])[CH2:35][S:32]([CH3:31])(=[O:34])=[O:33])[CH2:26]3)[O:19][CH2:18]4)=[N:12][CH2:11]2)[CH:4]=[C:3]([Cl:2])[CH:8]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 37328412-Methanesulfonylacetic acidHCID 90001298HCID 90001298, compound

Product 1

HCID 73505596HCID 73505596, compoundYield 74.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the stirred solution of 5′-(3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl)-3′H-spiro[azetidine-3,1′-isobenzofuran]hydrochloride (Preparation 13, 0.46 g, 0.963 mmol) in DMF (10 mL) was added TEA (0.67 mL, 4.81 mmol), methane sulfonyl acetic acid (0.266 g, 1.93 mmol) followed by addition of HOBt (0.13 g, 0.96 mmol) and EDC.HCl (0.276 g, 1.44 mmol) at room temperature. Resulting reaction mixture was stirred at room temperature for 16 hours. After complete conversion of starting material, reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (3×20 mL). Combined organic layer was washed with LiCl solution (2×40 mL) and brine (2×50 mL), dried over sodium sulfate and concentrated to get brown semi solid (0.597 g, crude). Crude compound was purified by column chromatography using silica gel (230-400 mesh). Desired compound was eluted in 0.8% methanol in DCM to get off white solid (403 mg). Compound was triturated thrice with chloroform n-hexane to get pure compound as off white solid (0.24 g, 44.4%), 1H NMR (400 MHz, DMSO-d6) δ: 3.14 (s, 3H), 3.73 (d, J=18.2 Hz, 1H), 3.87 (d, J=18.12 Hz, 1H), 4.23 (d, J=10.48 Hz, 4H), 4.42 (d, J=16.88 Hz, 1H), 4.57 (s, 2H), 4.82 (d, J=17.2 Hz, 1H), 5.13 (s, 2H), 7.57 (s, 2H), 7.65 (d, J=7.92 Hz, 1H), 7.70 (s, 1H), 7.86 (s, 1H), 7.95 (d, J=7.8 Hz, 1H), LC-MS (m/z): 561.0 (M+H),

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete conversion of starting material, reaction mixture
  4. customwas quenched with water (20 mL)
  5. extractionextracted with ethyl acetate (3×20 mL)
  6. washCombined organic layer was washed with LiCl solution (2×40 mL) and brine (2×50 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customto get brown semi solid (0.597 g, crude)
  10. customCrude compound was purified by column chromatography
  11. washDesired compound was eluted in 0.8% methanol in DCM

Sources & evidence

ORD record
ord-86982881e9354dd7868567609c074bef
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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