Triethylamine → HCID 86689156, compound

HRID 1752471Notes

Reaction equation

HRID 1752471 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:17])[C:13]([F:15])([F:14])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[C:5]([F:18])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:26][O:27][C:28]1[CH:49]=[CH:48][C:31]([C:32](Cl)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)=[CH:30][CH:29]=1>C(Cl)Cl>[CH3:40][O:39][C:36]1[CH:35]=[CH:34][C:33]([C:32]([NH:16][C:10]2[O:11][CH2:12][C:13]([F:14])([F:15])[C@:8]([C:6]3[C:5]([F:18])=[CH:4][CH:3]=[C:2]([Br:1])[N:7]=3)([CH3:17])[N:9]=2)([C:31]2[CH:30]=[CH:29][C:28]([O:27][CH3:26])=[CH:49][CH:48]=2)[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[CH:38][CH:37]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)HCID 86689157HCID 86689157, compound2×

Product 1

HCID 86689156HCID 86689156, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-4-(6-bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazine-2-ylamine (5 g, 15.43 mmol, Example 1 intermediate h) was dissolved in DCM (154 ml) under argon, triethylamine (4.30 mL, 30.9 mmol) and 4,4′-dimethoxytrityl chloride (5.75 g, 16.97 mmol) were added and the reaction mixture was stirred at rt for 18 hours. The solvent was removed in vacuo and the residue was taken up in ethyl acetate. The organic layer was washed with aq 10% citric acid, water, aqueous saturated sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and concentrated. The crude product was chromatographed over silica gel (Redisep column 120 g, cyclohexane/ethyl) to give the title compound: 8.16 g (69.2% yield).

Workup

  1. customThe solvent was removed in vacuo
  2. washThe organic layer was washed with aq 10% citric acid, water, aqueous saturated sodium bicarbonate solution and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was chromatographed over silica gel (Redisep column 120 g, cyclohexane/ethyl)

Sources & evidence

ORD record
ord-5324d19790594a9887e087e67e05ad1c
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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