Benzene, 2-bromo-1-chloro-4-methyl- → (+/-)-cis-N-(2-chloro-5-methylphenyl)-4,5,7,7a,8,9,10,10a-octahydrodipyrrolo[3,4-c:3',2',1'-ij]quinolin-2-amine

HRID 1836592Notes

Reaction equation

HRID 1836592 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH3:9])[CH:5]=[CH:6][C:7]=1[Cl:8].[NH2:10][C:11]1[CH:12]=[C:13]2[C:18]3=[C:19]([CH2:21][CH2:22][N:17]3[CH2:16][C@@H:15]3[CH2:23][N:24](C(OC(C)(C)C)=O)[CH2:25][C@H:14]23)[CH:20]=1>>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([CH3:9])=[CH:3][C:2]=1[NH:10][C:11]1[CH:12]=[C:13]2[C:18]3=[C:19]([CH2:21][CH2:22][N:17]3[CH2:16][C@@H:15]3[CH2:23][NH:24][CH2:25][C@H:14]23)[CH:20]=1

Participants

3

Reactant 2

HCID 284147Benzene, 2-bromo-1-chloro-4-methyl-HCID 131724549(+/-)-cis tert-butyl 2-amino-4,5,7a,8,10,10a-hexahydrodipyrrolo[3,4-c:3',2',1'-ij]quinoline-9(7H)-carboxylate

Product 1

HCID 68521681(+/-)-cis-N-(2-chloro-5-methylphenyl)-4,5,7,7a,8,9,10,10a-octahydrodipyrrolo[3,4-c:3',2',1'-ij]quinolin-2-amine

Procedure

Using 3-bromo-4-chlorotoluene and following the procedures described in EXAMPLE 17, Parts B and C, (±)-cis tert-butyl 2-amino-4,5,7a,8,10,10a-hexahydrodipyrrolo[3,4-c:3′,2′,1′-ij]quinoline-9(7H)-carboxylate was converted into (±)-cis-N-(2-chloro-5-methylphenyl)-4,5,7,7a,8,9,10,10a-octahydrodipyrrolo[3,4-c:3′,2′,1′-ij]quinolin-2-amine, bis-trifluoroacetic acid salt, after HPLC purification (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA). This material was free-based with aq ammonium hydroxide, extracted with chloroform, washed with brine, dried (K2CO3) and concentrated to the title compound of EXAMPLE 117 as the free base. 1H NMR (CDCl3) δ: 7.18 (d, 1H, J=8.0 Hz), 6.91 (s, 1H), 6.71 (app s, 2H), 6.52 (dd, 1H, J=8.0, 1.4 Hz), 5.83 (s, 1H), 3.79 (dd, 1H, J=11.4, 8.1 Hz), 3.63 (dd, 1H, J=11.5, 7.1 Hz), 3.54 (q, 1H, J=7.5 Hz), 3.37-3.22 (m, 3H), 3.15 (dd, 1H, J=11.3, 8.4 Hz), 3.08-2.92 (m, 4H), 2.85 (dd, 1H, J=10.4, 7.5 Hz). LRMS (ES)+: 340.3 (M+H)+.

Workup

  1. customafter HPLC purification (C18
  2. washphase column, elution with a H2O/CH3CN gradient with 0.5% TFA)
  3. extractionextracted with chloroform
  4. washwashed with brine
  5. dry with materialdried (K2CO3)
  6. concentrationconcentrated to the title compound of EXAMPLE 117 as the free base

Sources & evidence

ORD record
ord-18bd2bf59c744fafbf73b9c178fbbf64
Source dataset
uspto-grants-2004_08
Patent number
US06777406B2

Reaction notes

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