Trifluoroacetic acid → HCID 69751389, compound

HRID 497470Notes

Reaction equation

HRID 497470 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C@@H:11]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]3[N:28]([CH3:29])[N:27]=[N:26][N:25]=3)[CH:19]=2)=[O:16])[C@H:10]([CH2:30][N:31]2[CH2:36][CH2:35][CH2:34][C@@H:33]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH2:32]2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:44][C:41]1[CH:42]=[CH:43][C:38]([CH2:37][C@@H:33]2[CH2:34][CH2:35][CH2:36][N:31]([CH2:30][C@H:10]3[C@H:11]([NH:14][C:15]([NH:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]5[N:28]([CH3:29])[N:27]=[N:26][N:25]=5)[CH:19]=4)=[O:16])[CH2:12][CH2:13][NH:8][CH2:9]3)[CH2:32]2)=[CH:39][CH:40]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69751615HCID 69751615, compound

Product 1

HCID 69751389HCID 69751389, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a dry flask (3R,4R)-3-[(S)-3-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-4-{3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-ureido}-piperidine-1-carboxylic acid t-butyl ester (48 mg, 0.079 mmol) was dissolved in dichloromethane (1.5 mL), and trifluoroacetic acid (0.5 mL) was added. The reaction mixture was stirred for 3 hours. The reaction mixture was concentrated in vacuo then purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid) to give a white amorphous solid (22 mg, 38%). 1H NMR (500 MHz, CD3OD, 30° C.), δ: 8.01 (t, 1H, J=1), 7.59 (dq, 1H, J=8, J′=1), 7.52 (t, 1H, J=8), 7.43 (dt, 1H, J=8, J=1), 7.17 (m, 2H), 6.96 (t, 2H, J=9), 4.18 (s, 3H), 3.73 (m, 2H), 3.51 (m, 3H), 3.38 (d, 1H, J=13), 3.13 (m, 2H), 2.99 (m, 2H), 2.64 (dd, 2H, J=14, J′=6), 2.50 (bs, 2H), 2.21 (m, 1H), 2.11 (bs, 1H), 1.92 (m, 2H), 1.76 (m, 2H), 1.19 (m, 1H). HRMS (ESI), C27H36FN8O m+/z: calc. 507.2996, found=507.2976.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthen purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-4b6d30738864437e99887b2e32a95bc9
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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