4-Fluorobenzylamine → HCID 59060800, compound

HRID 47685Notes

Reaction equation

HRID 47685 reaction equation
[CH3:1][C:2]([Si:5]([CH3:46])([CH3:45])[O:6][C@H:7]([CH2:37][O:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:8][N:9]([CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([C:34]([OH:36])=O)[CH:29]=3)[CH:24]=2)[O:19]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:4])[CH3:3].[F:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][NH2:53])=[CH:50][CH:49]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>ClCCl>[CH3:1][C:2]([Si:5]([CH3:45])([CH3:46])[O:6][C@H:7]([CH2:37][O:38][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[CH2:8][N:9]([CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([C:34]([NH:53][CH2:52][C:51]4[CH:54]=[CH:55][C:48]([F:47])=[CH:49][CH:50]=4)=[O:36])[CH:29]=3)[CH:24]=2)[O:19]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 673264-FluorobenzylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59060782HCID 59060782, compound

Product 1

HCID 59060800HCID 59060800, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a solution of 4-((2R)-2-{[[(2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(phenyloxy)propyl](phenylmethyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)-2-pyridinecarboxylic acid (Example 90, 82 mg, 0.13 mmol) in dichloromethane (2 mL) was added 4-fluorobenzylamine (33 mg, 0.26 mmol, 2.0 eq.), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (50 mg, 0.26 mmol, 2.0 eq.), and 1-hydroxybenzotriazole (35 mg, 0.26 mmol, 2.0 eq.). The solution was stirred overnight at room temperature before being concentrated in vacuo to remove volatile components. The crude residue was purified by flash chromatography on silica gel eluted with 75:25 hexanes/ethyl acetate. The title compound was obtained as a yellow oil (34 mg, 35%): 1H NMR (300 MHz, CDCl3) δ8.47 (d, 1 H), 8.40 (s, 2 H), 7.55 (dd, 1 H), 7.44-7.39 (m, 2 H), 7.34-7.29 (m, 4 H), 7.25-7.20 (m, 4 H), 7.01 (t, 2 H), 6.93-6.80 (m, 4 H), 4.64 (d, 2 H), 4.22-4.16 (m, 1 H), 4.11-4.05 (m, 1 H), 3.83 (s, 2 H), 3.75 (dd, 1 H), 2.94-2.80 (m, 2 H), 2.73-2.67 (m, 4 H), 1.71-1.57 (m, 2 H), 0.86 (s, 9H), 0.09 (s, 3 H), 0.05 (s, 3 H); MS m/z 746.5 (M+).

Workup

  1. concentrationbefore being concentrated in vacuo
  2. customto remove volatile components
  3. customThe crude residue was purified by flash chromatography on silica gel
  4. washeluted with 75:25 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-82f5dfcba61740fbbfb2033b0c4aa94d
Source dataset
uspto-grants-2004_03
Patent number
US06699860B2

Reaction notes

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