o-(Trifluoromethyl)benzaldehyde → (+/-)-cis-N-[2-(trifluoromethyl)benzyl]-4,5,7,7a,8,9,10,10a-octahydrodipyrrolo[3,4-c:3',2',1'-ij]quinolin-2-amine

HRID 1836594Notes

Reaction equation

HRID 1836594 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]=O.[NH2:13][C:14]1[CH:15]=[C:16]2[C:21]3=[C:22]([CH2:24][CH2:25][N:20]3[CH2:19][C@@H:18]3[CH2:26][N:27](C(OC(C)(C)C)=O)[CH2:28][C@H:17]23)[CH:23]=1>>[F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][NH:13][C:14]1[CH:15]=[C:16]2[C:21]3=[C:22]([CH2:24][CH2:25][N:20]3[CH2:19][C@@H:18]3[CH2:26][NH:27][CH2:28][C@H:17]23)[CH:23]=1

Participants

3

Reactant 2

HCID 123067o-(Trifluoromethyl)benzaldehydeHCID 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 68522619(+/-)-cis-N-[2-(trifluoromethyl)benzyl]-4,5,7,7a,8,9,10,10a-octahydrodipyrrolo[3,4-c:3',2',1'-ij]quinolin-2-amine

Procedure

Using 2-(trifluoromethyl)benzaldehyde and following the procedures described in EXAMPLE 76, (±)-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-(trifluoromethyl)benzyl]-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 119 as the free base. 1H NMR (CDCl3) δ: 7.69 (d, 1H, J=7.7 Hz), 7.65 (d, 1H, J=7.7 Hz), 7.51 (t, 1H, J=7.4 Hz), 7.37 (t, 1H, J=7.7 Hz), 6.42 (d, 1H, J=1.4 Hz), 6.14 (d, 1H, J=1.8 Hz), 4.47 (s, 2H), 3.70 (dd, 1H, J=11.4, 8.1 Hz), 3.56 (dd, 1H, J=11.9, 7.5 Hz), 3.45 (q, 1H, J=7.7 Hz), 3.28-3.10 (m, 3H), 3.05 (dd, 1H, J=11.5, 8.3 Hz), 2.97-2.85 (m, 4H), 2.72 (dd, 1H, J=11.5, 8.6 Hz). LRMS (ES)+: 374.3 (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 119 as the free base

Sources & evidence

ORD record
ord-09d879563bf2410c9cd0dd4949cd03d2
Source dataset
uspto-grants-2004_08
Patent number
US06777406B2

Reaction notes

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