4,6-Dichloro-pyrimidine-5-carbonyl chloride → N-(1-Allyl-2-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamide

HRID 576571Notes

Reaction equation

HRID 576571 reaction equation
[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([NH:13][CH2:14][CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])=[CH:10][CH:11]=2)[C:6](=[O:24])[N:5]1[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH:2]=[CH2:3].[Cl:32][C:33]1[C:38]([C:39](Cl)=[O:40])=[C:37]([Cl:42])[N:36]=[CH:35][N:34]=1>C(Cl)Cl>[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([N:13]([CH2:14][CH2:15][O:16][Si:17]([C:20]([CH3:22])([CH3:23])[CH3:21])([CH3:18])[CH3:19])[C:39]([C:38]3[C:33]([Cl:32])=[N:34][CH:35]=[N:36][C:37]=3[Cl:42])=[O:40])=[CH:10][CH:11]=2)[C:6](=[O:24])[N:5]1[CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 121633604,6-Dichloro-pyrimidine-5-carbonyl chlorideHCID 867126101-Allyl-2-benzyl-5-(2-(tert-butyldimethylsilyloxy)ethylamino)-1H-indazol-3(2H)-one

Product 1

HCID 86712609N-(1-Allyl-2-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamideYield 46.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred, cooled (0° C.) solution of product of 11E (0.55 g, 1.23 mmol) and TEA (0.5 g, 5.0 mmol) in DCM (12 mL) was added drop wise a solution of 4,6-dichloropyrimidine-5-carbonyl chloride (0.26 g, 1.23 mmol) in DCM (5 mL). After 6 h, the reaction was concentrated in vacuo, diluted with ethyl acetate, and washed with water (2×10 mL) and saturated aqueous brine. The organic layer was dried over sodium sulphate, filtered and concentrated in vacuo to afford oil. The residue was purified by flash chromatography using 12% ethyl acetate in hexane as eluent to afford title compound (0.35 g, 46%) as an oil. 1H NMR (400 MHz, DMSO-d6): δ 8.75 (s, 1H), 7.75 (s, 1H), 7.46 (m, 3H), 7.36 (m, 4H), 5.94 (m, 1H), 5.34 (s, 2H), 5.08 (m, 1H), 4.96 (m, 1H), 4.82 (m, 2H), 4.0 (m, 2H), 3.77 (t, J=4.8 Hz, 2H), 0.8 (s, 9H), 0.01 (s, 6H); ESI-MS m/z=611 (M+H)+.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. washwashed with water (2×10 mL) and saturated aqueous brine
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford oil
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-0544955b68144e32be58b4100f5152e0
Source dataset
uspto-grants-2015_05
Patent number
US09040517B2

Reaction notes

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