Trifluoroacetic acid → HCID 11091606, compound

HRID 488765Notes

Reaction equation

HRID 488765 reaction equation
C1C2C(=CC=CC=2)CC(C(O)=O)N1.O[C:15]1[CH:24]=[C:23]2[C:18]([CH2:19][C@@H:20]([C:25]([NH:27][C@H:28]([CH2:32][N:33]3[CH2:38][CH2:37][C@:36]([C:40]4[CH:45]=[CH:44][CH:43]=[C:42]([OH:46])[CH:41]=4)([CH3:39])[C@@H:35]([CH3:47])[CH2:34]3)[CH:29]([CH3:31])[CH3:30])=[O:26])[NH:21][CH2:22]2)=[CH:17][CH:16]=1.C(O)(C(F)(F)F)=O>>[OH:46][C:42]1[CH:41]=[C:40]([C@:36]2([CH3:39])[CH2:37][CH2:38][N:33]([CH2:32][C@@H:28]([NH:27][C:25]([C@H:20]3[CH2:19][C:18]4[C:23](=[CH:24][CH:15]=[CH:16][CH:17]=4)[CH2:22][NH:21]3)=[O:26])[CH:29]([CH3:31])[CH3:30])[CH2:34][C@@H:35]2[CH3:47])[CH:45]=[CH:44][CH:43]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 954891,2,3,4-Tetrahydroisoquinoline-3-carboxylic acidHCID 11145065HCID 11145065, compound

Product 1

HCID 11091606HCID 11091606, compound

Procedure

3-[1-(2S-Amino-3-methylbutyl)-3R,4R-dimethyl-4-piperidinyl]phenol (23) was coupled to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid as described for compound 15 and de-protected with TFA as previously described to give crude product which was purified by silica preparative thin layer chromatography (50% (CHCl3:MeOH:NH4OH, 80:18:2) in CHCl3, yielding 0.028 g (3R)-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (16). 1H NMR (CDCl3): 7.22 (d, J=8.8 Hz, 1H), 7.05-7.13 (m, 3H), 6.98-7.01 (m, 1H), 6.79 (s, 1H), 6.73 (d, J=7.8 Hz, 1H), 6.65 (dd, J=7.9, 1.8 Hz, 1H), 4.05-4.14 (m, 1H), 3.99 (s, 2H), 3.56 (dd, J=10.7, 4.9 Hz, 1H), 3.18 (dd, J=16.5,4.8 Hz, 1H), 2.67-2.82 (m, 3H), 2.31-2.54 (m, 4H), 2.18-2.25 (m, 1H), 1.86-1.96 (m, 2H), 1.52 (d, J=12.9 Hz, 1H), 1.25 (s, 3H), 0.92 (t, J=7.6 Hz, 6H), 0.67 (d, J=6.9 Hz, 3H). LRMS (ES) m/z 450.3.2 (M+H)+.

Workup

  1. customto give crude product which
  2. customwas purified by silica preparative thin layer chromatography (50% (CHCl3:MeOH:NH4OH, 80:18:2) in CHCl3

Sources & evidence

ORD record
ord-d30b845d15cc40678fba92812a996882
Source dataset
uspto-grants-2005_12
Patent number
US06974824B2

Reaction notes

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