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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 921004
Notes
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Reaction equation

HRID 921004 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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 6344Dichloromethane
Solvent
2×

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-1f82192e266746f7a399740fcccb4f80
Source dataset
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09273069B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes