tert-Butyl isocyanate → 4-[2-(3-tert-Butyl-ureido)-2-phenyl-acetyl]-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

HRID 2075778Notes

Reaction equation

HRID 2075778 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:41])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:29][O:28][CH2:27][CH2:26][N:25]4[C:30](=[O:39])[CH:31]([NH2:38])[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][N:10]([CH3:40])[N:9]=2)[CH:7]=1.[C:42]([N:46]=[C:47]=[O:48])([CH3:45])([CH3:44])[CH3:43]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:41])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:29][O:28][CH2:27][CH2:26][N:25]4[C:30](=[O:39])[CH:31]([NH:38][C:47]([NH:46][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:48])[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][N:10]([CH3:40])[N:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 62412tert-Butyl isocyanateHCID 1363466894-(2-Amino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

Product 1

HCID 1363466914-[2-(3-tert-Butyl-ureido)-2-phenyl-acetyl]-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 9D (4.0 g, 7.02 mmol) in anhydrous CH2Cl2 (100 mL) was added tert-butyl isocyanate (12D, 3.21 mL, 28.07 mmol). The reaction mixture was stirred at rt overnight. It was concentrated to small volume and purified with silica column chromatography eluting with dichloromethane/EtOAc to give the title compound (13D) as white powder in good yield. 1H NMR (CDCl3, 500 MHz) δ 10.68 (s, 1H), 8.92 (s, 1H), 8.72 (s, 1H), 8.02 (d, 2H, J=8.0 Hz), 7.63 (s, 1H), 7.56 (d, 2H, J=8.0 Hz), 7.38 (s, 5H), 7.19 (d, 1H, J=8.0 Hz), 6.96 (d, 1H, J=8.5 Hz), 5.58 (d, 1H, J=6.0 Hz), 5.30 (s, 1H), 5.18 (d, 1H, J=6.5 Hz), 4.85 (d, 1H, J=11.5 Hz), 4.79 (s, 1H), 3.96 (s, 3H), 3.79 (d, 1H, J=11.5 Hz), 3.62 (br s, 2H), 3.44 (d, 1H, J=10.0 Hz), 3.11 (m, 1H), 1.29 (s, 9H). LCMS (ESI) m/z 669.25 (MH+), 570.23 (100). HPLC: tR=5.22 min.

Workup

  1. concentrationIt was concentrated to small volume
  2. custompurified with silica column chromatography
  3. washeluting with dichloromethane/EtOAc

Sources & evidence

ORD record
ord-bc08d245c8694f8a81b2f65c90cfad51
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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