Diisopropylethylamine → HCID 73505386, compound

HRID 1508294Notes

Reaction equation

HRID 1508294 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:11]2([C:28]([F:31])([F:30])[F:29])[CH2:15][C:14]([C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[C:21]3([CH2:27][NH:26][CH2:25]3)[O:20][CH2:19]4)=[N:13][CH2:12]2)[CH:6]=[C:7]([Cl:10])[C:8]=1[Cl:9].CCN(C(C)C)C(C)C.[CH3:41][S:42]([CH2:45][C:46](O)=[O:47])(=[O:44])=[O:43].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C1COCC1>[CH3:41][S:42]([CH2:45][C:46]([N:26]1[CH2:25][C:21]2([C:22]3[C:18](=[CH:17][C:16]([C:14]4[CH2:15][C:11]([C:5]5[CH:4]=[C:3]([Cl:2])[C:8]([Cl:9])=[C:7]([Cl:10])[CH:6]=5)([C:28]([F:30])([F:29])[F:31])[CH2:12][N:13]=4)=[CH:24][CH:23]=3)[CH2:19][O:20]2)[CH2:27]1)=[O:47])(=[O:44])=[O:43]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 37328412-Methanesulfonylacetic acidHCID 90001071HCID 90001071, compound

Product 1

HCID 73505386HCID 73505386, compoundYield 46.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5′-(3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl)-3′H-spiro[azetidine-3,1′-isobenzofuran]hydrochloride (Preparation 5, 900 mg, 1.77 mmol) in THF (20 mL) was added DIPEA (3.01 mL, 17.65 mmol), methanesulfonyl acetic acid (488 mg, 3.53 mmol) followed by addition of T3P (5.12 mL, 8.82 mmol, 50% solution in ethyl acetate) at room temperature. The resulting reaction mixture was stirred at room temperature for 16 hours. Reaction was monitored by TLC, after complete consumption of staring material reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (3×25 mL). Combined organic layer was washed with NaHCO3 solution (30 mL) & brine (30 mL), dried over sodium sulphate and concentrated to get crude sticky solid 1 g. The crude was purified by column chromatography using 100-200 mesh silica gel. Desired compound was eluted in 0.5% MeOH in DCM to get desired compound as pale green solid 490 mg, 46.6%. 1H NMR (400 MHz, DMSO-d6) δ: 3.14 (s, 3H), 3.75 (d, J=18.04 Hz, 1H), 3.88 (d, J=18.52 Hz, 1H), 4.23 (d, J=10.36 Hz, 4H), 4.44 (d, J=17.6 Hz, 1H), 4.57 (s, 2H), 4.82 (d, J=17.4 Hz, 1H), 5.10 (s, 2H), 7.66 (d, J=7.96 Hz, 1H), 7.80 (s, 2H), 7.86 (s, 1H), 7.95 (d, J=7.96 Hz, 1H). LC-MS (m/z): 594.8 (M+H).

Workup

  1. customThe resulting reaction mixture
  2. customReaction
  3. customafter complete consumption of staring material reaction mixture
  4. customwas quenched with water (30 mL)
  5. extractionextracted with ethyl acetate (3×25 mL)
  6. washCombined organic layer was washed with NaHCO3 solution (30 mL) & brine (30 mL)
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated
  9. customto get crude sticky solid 1 g
  10. customThe crude was purified by column chromatography
  11. washDesired compound was eluted in 0.5% MeOH in DCM

Sources & evidence

ORD record
ord-7a3a7179fb10469dbb3fe00cd4b5da77
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

Loading…