Tris(hydroxymethyl)aminomethane → HCID 66689643, compound

HRID 403534Notes

Reaction equation

HRID 403534 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10]2[CH:20]([NH:22]C)[CH3:21])=[CH:5][CH:4]=1.[C:24]([C:28]1[CH:33]=[CH:32][C:31]([S:34](Cl)(=[O:36])=[O:35])=[CH:30][CH:29]=1)([CH3:27])([CH3:26])[CH3:25].[CH2:38](O)C(N)(CO)CO>C(Cl)Cl>[C:24]([C:28]1[CH:33]=[CH:32][C:31]([S:34]([NH:22][CH:20]([C:10]2[N:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH3:21])(=[O:36])=[O:35])=[C:30]([CH3:38])[CH:29]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 1398824-t-Butylbenzenesulfonyl chlorideHCID 66690203HCID 66690203, compound

Product 1

HCID 66689643HCID 66689643, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of the 3-(4-methoxyphenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one (50 mg, 0.16 mmol) stirring in 2 mL DCM was added TEA (19 mg, 0.19 mmol) followed by the addition of neat 4-tert-butyl-benzenesulfonyl chloride (37 mg, 0.16 mmol). The reaction was allowed to stir at room temperature for 2 h then treated with PS-tris-amine resin (100 mg). The reaction was allowed to stand for 15 min at room temperature after which the resin was removed by filtration. The filtrate was concentrated under vacuum to afford the crude product. The crude residue was purified by flash chromatography (silica gel, 50% EtOAc/Hex) to afford the desired product as an off-white powder (74 mg, 92% yield). 1H-NMR (CDCl3): δ 8.15 (d, 1H), 7.55 (s, 1H), 7.39 (m, 4H), 7.25 (d, 1H), 7.16 (m, 2H), 7.09 (m, 1H), 6.70 (m, 2H), 4.90 (q, 1H), 4.83 (s, 3H), 3.11 (s, 3H), 1.22 (d, 3H), 1.09 (s, 9H); MS (ESI) 506 (MH+).

Workup

  1. waitto stand for 15 min at room temperature
  2. customafter which the resin was removed by filtration
  3. concentrationThe filtrate was concentrated under vacuum
  4. customto afford the crude product
  5. customThe crude residue was purified by flash chromatography (silica gel, 50% EtOAc/Hex)

Sources & evidence

ORD record
ord-142444cb0e1a4bceb86d6352c50b0d95
Source dataset
uspto-grants-2014_06
Patent number
US08748440B2

Reaction notes

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