Valeryl chloride → HCID 19783157, compound

HRID 257559Notes

Reaction equation

HRID 257559 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:48])=[C:6]([N:8]2[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:11]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[S:31](=[O:43])(=[O:42])[NH:32][C:33](=[O:41])[C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[Cl:40])=[CH:21][CH:20]=3)[C:10]([CH2:44][CH2:45][CH2:46][CH3:47])=[N:9]2)[CH:7]=1.[C:49](Cl)(=[O:54])[CH2:50][CH2:51][CH2:52][CH3:53]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[CH2:44]([C:10]1[C:11]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[S:31](=[O:42])(=[O:43])[NH:32][C:33](=[O:41])[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[Cl:40])=[CH:23][CH:24]=2)=[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:8]([C:6]2[CH:7]=[C:2]([NH:1][C:49](=[O:54])[CH2:50][CH2:51][CH2:52][CH3:53])[CH:3]=[CH:4][C:5]=2[Cl:48])[N:9]=1)[CH2:45][CH2:46][CH3:47]

Participants

5

Reactant 2

HCID 61186Valeryl chlorideHCID 19783146HCID 19783146, compound

Product 1

HCID 19783157HCID 19783157, compoundYield 73.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

To a mixture of 150 mg (0.213 mmol) of ethyl 1-(5-amino-2-chlorophenyl)-3-n-butyl-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]-biphenyl-4-yl]methyl]-1H-pyrazole-5-carboxylate (from Step I), 26 mg (0.213 mmol) of 4-(dimethylamino)pyridine (DMAP), and 1.75 mL of dry pyridine was added 126 μL (128 mg, 1.06 mmol) of valeryl chloride. The mixture was stirred under N2 at room temperature overnight and then partitioned between H2O and ethyl acetate. The organic layer was washed twice with H2O and then with brine. Next, the ethyl acetate phase was dried over Na2SO4, filtered, and rotary-evaporated in vacuo. The yellow-orange residual oil was flash chromatographed on silica gel (gradient elution with 0.5-3% MeOH in CH2Cl2) to give 123 mg (72%) of the title compound as a slightly yellow solid, mp>95° C. (gradual); homogeneous by TLC in 95:5 CH2Cl2 -- MeOH; mass spectrum (FAB) m/e 827 (M+K)+. 400 MHz 1H NMR (CDCl3) δ0.87 (t, J=7.3 Hz, 3H), 0.92 (t, J=7.4 Hz, 3H), 1.02 (t, J=7.1 Hz, 3H), 1.29-1.40 (m, 4H), 1.57 (m, 2H), 1.67 (m, 2H), 2.32 (t, J=7.6 Hz, 2H), 2.53 (t, J=7.8 Hz, 2H), 4.05-4.15 (m, 4H), 7.06 (d, J=8.2 Hz, 2H), 7.21-7.66 (m, 10H), 7.75 (d, J=2.4 Hz, 1H), 8.27 (s, 1H), 8.34 (dd, J=8.0, 1.3 Hz, 1H).

Workup

  1. custompartitioned between H2O and ethyl acetate
  2. washThe organic layer was washed twice with H2O
  3. dry with materialNext, the ethyl acetate phase was dried over Na2SO4
  4. filtrationfiltered
  5. customrotary-evaporated in vacuo
  6. customchromatographed on silica gel (gradient elution with 0.5-3% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-f5f7edc12d1a4f9d95d3aa38c0bcfecb
Source dataset
uspto-grants-1993_11
Patent number
US05262412

Reaction notes

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