Triethylamine → HCID 21362412, compound

HRID 1169225Notes

Reaction equation

HRID 1169225 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]([NH:13][C@@H:14]2[CH2:19][CH2:18][NH:17][CH2:16][C@@H:15]2[CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:22]2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].C(N(CC)CC)C.[C:42](Cl)(=[O:47])[C:43]([CH3:46])([CH3:45])[CH3:44]>ClCCl>[C:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]([NH:13][C@@H:14]2[CH2:19][CH2:18][N:17]([C:42](=[O:47])[C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:16][C@H:15]2[CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[CH2:22]2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 69749732HCID 69749732, compound

Product 1

HCID 21362412HCID 21362412, compoundYield 46.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a dry flask 1-(3-acetyl-phenyl)-3-{(3R,4R)-3-[(S)-3-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-piperidin-4-yl}-urea (43 mg, 0.07 mmol) was dissolved in dichloromethane (2 mL), and then triethylamine (65 μL, 0.47 mmol) and pivaloyl chloride (12 μL, 0.10 mmol) were added. The reaction mixture was stirred for 17 hours. The reaction mixture was concentrated in vacuo then was purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid) to give a white amorphous solid (18 mg, 38%). 1H NMR (300 MHz, CD3OD), δ: 8.04 (s, 1H), 7.64 (d, 1H, J=7), 7.58 (dd, 1H, J=7, J′=1), 7.40 (t, 1H, J=8), 7.19 (m, 2H), 6.99 (t, 2H, J=9), 4.27 (d, 1H, J=14), 4.14 (d, 1H, J=15), 3.71 (m, 1H), 3.48 (bm, 3H), 3.25 (m, 2H), 3.07 (m, 1H), 2.95 (m, 2H), 2.66 (m, 2H), 2.57 (s, 3H), 1.98 (m, 4H), 1.76 (m, 2H), 1.62 (m, 1H), 1.28 (s, 9H), 1.20 (m, 1H). HRMS (ESI), C32H44FN4O3 m+/z: calc. 551.3397, found=551.3402.

Workup

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

Sources & evidence

ORD record
ord-ca1829beb1ee41429b9e482a802edf63
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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