Isobutyryl chloride → HCID 11720881, compound

HRID 1986628Notes

Reaction equation

HRID 1986628 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([N:12]([CH2:24][CH2:25][CH2:26][N:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=3)=[O:14])[CH2:9]2)=[CH:4][CH:3]=1.[C:34](Cl)(=[O:38])[CH:35]([CH3:37])[CH3:36].CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:13](=[O:14])[N:12]([CH:8]2[CH2:9][C:10]3[CH:11]=[C:2]([NH:1][C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])[CH:3]=[CH:4][C:5]=3[CH2:6][CH2:7]2)[CH2:24][CH2:25][CH2:26][N:27]2[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]2)[CH:21]=[CH:20][C:19]=1[F:22]

Participants

5

Reactant 3

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 44417989HCID 44417989, compound

Product 1

HCID 11720881HCID 11720881, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(7-amino-1,2,3,4-tetrahydro-naphthalen-2-yl)-3-(3-chloro-4-fluoro-phenyl)-1-[3-(4-methyl-piperazin-1-yl)-propyl]-urea (Preparative Example 27, 0.020 g, 0.042 mmol) in CH2Cl2 (0.2 mL) at 0° C. were added isobutyryl chloride (0.0054 mL, 0.052 mmol) and DIEA (0.026 mL, 0.15 mmol). After stirring from 0° C. to room temperature for 16 hours, the mixture was concentrated in vacuo and the residue was purified by preparative HPLC to give 0.020 g (88%) of N-(7-{3-(3-chloro-4-fluoro-phenyl)-1-[3-(4-methyl-piperazin-1-yl)-propyl]-ureido}-5,6,7,8-tetrahydro-naphthalen-2-yl)-isobuty ramide as a light yellow gum. 1H NMR (300 MHz, CD3OD): δ 7.60 (dd, 1H, J=6.9, 2.4 Hz), 7.40 (d, 1H, J=2.1 Hz), 7.30 (ddd, 1H, J=9.0, 4.2, 2.4 Hz), 7.20 (dd, 1H, J=8.4, 2.1 Hz), 7.15 (t, 1H, J=9.0 Hz), 7.05 (d, 1H, J=8.4 Hz), 4.31 (m, 1H), 3.62 (m, 8H), 3.49 (m, 2H), 3.27 (t, 2H, J=6.9 Hz), 2.98 (m, 7H), 2.10 (m, 4H), 1.38 (dd, 1H, J=6.6, 2.7 Hz), 1.19 (d, 6H, J=6.6 Hz). MS-ESI: 544.1 (M+H+).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-8ed060450bcd4234af54620646d5fcf5
Source dataset
uspto-grants-2009_06
Patent number
US07550467B2

Reaction notes

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