Sodium Bicarbonate → tert-butyl ((3R,4S)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)tetrahydrofuran-3-yl)carbamate

HRID 56368

Reaction equation

HRID 56368 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[C:17]([Cl:18])=[C:16]([O:19][CH3:20])[CH:15]=[C:14]([O:21][CH3:22])[C:13]=3[Cl:23])[CH:8]=2)[N:3]=1.[NH2:24][C@@H:25]1[CH2:29][O:28][CH2:27][C@@H:26]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34].C(=O)(O)[O-].[Na+]>CN1C(=O)CCC1>[Cl:18][C:17]1[C:16]([O:19][CH3:20])=[CH:15][C:14]([O:21][CH3:22])=[C:13]([Cl:23])[C:12]=1[C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([NH:24][C@@H:25]1[CH2:29][O:28][CH2:27][C@@H:26]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[N:11]=[CH:10]2

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 899217722-Chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolineHCID 90436776tert-butyl ((3R,4S)-4-aminotetrahydrofuran-3-yl)carbamate

Product 1

HCID 118043440tert-butyl ((3R,4S)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)tetrahydrofuran-3-yl)carbamateYield 74.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2-chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazoline (1.02 g, 2.76 mmol), tert-butyl ((3R,4S)-4-aminotetrahydrofuran-3-yl)carbamate (0.85 g, 4.20 mmol), and sodium bicarbonate (0.58 g, 6.90 mmol) was stirred in NMP (5.5 mL, 0.5M) at 95° C. for 12 hours. The reaction was removed from the oil bath and while cooling to room temperature was treated with about 90 mL of water and then sonicated and stirred for 20 minutes. A yellow-orange solid was isolated by filtration, rinsed several times with small amounts of water, and dried under vacuum for nearly 1 hour to yield 3.35 g of crude, which was purified by silica gel chromatography to yield 1.10 g (74.5% yield) of tert-butyl ((3R,4S)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)tetrahydrofuran-3-yl)carbamate as a light yellow foam. MS (ES+) C25H28Cl2N4O5 requires: 534, found: 535 [M+H]+.

Workup

  1. customThe reaction was removed from the oil bath
  2. additionwas treated with about 90 mL of water
  3. customsonicated
  4. customA yellow-orange solid was isolated by filtration
  5. washrinsed several times with small amounts of water
  6. customdried under vacuum for nearly 1 hour
  7. customto yield 3.35 g of crude, which
  8. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-dd24e3903a2548b6a8085bfc0b373487
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Linked notes

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