L-(+)-Cysteine → 2-(7-(3-Cyano-4-isopropoxybenzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

HRID 1964141Notes

Reaction equation

HRID 1964141 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][CH:33]([CH3:35])[CH3:34])[CH2:6][O:7][C:8]1[CH:16]=[CH:15][C:14]2[N:13]3[CH2:17][CH2:18][CH:19]([CH2:20][C:21]([O:23]C(C)(C)C)=[O:22])[C:12]3=[C:11]([CH3:28])[C:10]=2[CH:9]=1)#[N:2].C(S)[C@H](N)C(O)=O.C(O)(C(F)(F)F)=O>CCOCC.C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][CH:33]([CH3:35])[CH3:34])[CH2:6][O:7][C:8]1[CH:16]=[CH:15][C:14]2[N:13]3[CH2:17][CH2:18][CH:19]([CH2:20][C:21]([OH:23])=[O:22])[C:12]3=[C:11]([CH3:28])[C:10]=2[CH:9]=1)#[N:2]

Participants

6

Reactant 3

HCID 5862L-(+)-CysteineHCID 6422Trifluoroacetic acidHCID 67249930tert-Butyl 2-(7-(3-Cyano-4-isopropoxybenzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 583296132-(7-(3-Cyano-4-isopropoxybenzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic AcidYield 110.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a pre-cooled flask containing tert-butyl 2-(7-(3-cyano-4-isopropoxybenzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (0.308 g, 0.649 mmol) was added a pre-cooled solution of D/L-2-Amino-3-mercaptopropanoic acid (0.079 g, 0.649 mmol) in TFA (6.49 mL, 0.649 mmol) at 0° C. After stirring for 3 h at 0° C., ice-cold water (65 mL) was added. The resulting suspension was diluted with Et2O (130 mL). The organic layer was separated, washed with water (2×30 mL), brine (30 mL), and dried over MgSO4. The solvent was coevaporated with toluene (25 mL) in vacuo at 25° C. The residue was coevaporated with toluene (20 mL) again to give an oil. The oil was dissolved in DCM (5 mL) and coevaporated with hexanes (25 mL) to give the title compound as a grey solid (0.299 g). LCMS m/z=419.4 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.32 (d, J=6.06 Hz, 6H), 2.16 (s, 3H), 2.19-2.29 (m, 1H), 2.47 (d, J=6.69 Hz, 1H), 2.70-2.82 (m, 2H), 3.54-3.65 (m, 1H), 3.92 (m, 1H), 4.03 (dt, J=8.05, 1.91 Hz, 1H), 4.79 (dt, J=12.13, 6.06 Hz, 1H), 5.04 (s, 2H), 6.74 (dd, J=8.72, 2.40 Hz, 1H), 7.00 (d, J=2.40 Hz, 1H), 7.13 (d, J=8.72 Hz, 1H), 7.28 (d, J=8.84 Hz, 1H), 7.72 (dd, J=8.78, 2.21 Hz, 1H), 7.78 (d, J=2.15 Hz, 1H), 12.27 (bs, 1H).

Workup

  1. customThe organic layer was separated
  2. washwashed with water (2×30 mL), brine (30 mL)
  3. dry with materialdried over MgSO4
  4. customwas coevaporated with toluene (25 mL) in vacuo at 25° C
  5. customto give an oil

Sources & evidence

ORD record
ord-709a1a6bef5a4b43b8500e5058538e20
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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