Dichloromethane → Ammonia methanol dichloromethane

HRID 1878601Notes

Reaction equation

HRID 1878601 reaction equation
[C:1]([O:5]C(=O)[NH:7][CH2:8][CH2:9][C:10](=[O:34])[NH:11][C:12]1[CH:13]=[N:14][CH:15]=[C:16]([C:18]2[C:19]3[CH:33]=[CH:32][NH:31][C:20]=3[N:21]=[C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)[N:23]=2)[CH:17]=1)(C)(C)C.C(O)(C(F)(F)F)=O.[CH2:43]([Cl:45])[Cl:44]>>[CH2:43]([Cl:45])[Cl:44].[CH3:1][OH:5].[NH3:7].[NH2:7][CH2:8][CH2:9][C:10]([NH:11][C:12]1[CH:13]=[N:14][CH:15]=[C:16]([C:18]2[C:19]3[CH:33]=[CH:32][NH:31][C:20]=3[N:21]=[C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)[N:23]=2)[CH:17]=1)=[O:34]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 68759377HCID 68759377, compound2×

Product 2

HCID 21584172Ammonia methanol dichloromethaneHCID 68739403HCID 68739403, compound

Procedure

A solution of (2-{5-[2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyridin-3-ylcarbamoyl}-ethyl)-carbamic acid tert-butyl ester (Intermediate 59) (1 eq, 1.54 mmol, 774 mg) in DCM (100 ml) is cooled to 5° C. using an ice bath. Then TFA (20 eq, 32.7 mmol, 2.52 ml) is added within 5 min, the cooling bath is removed, and the mixture is stirred for 1 h at r.t. After addition of saturated aqueous K2CO3 solution the layers are separated and the aqueous layer is concentrated. The residue is taken up in MeCN, filtered, and the filtrate is concentrated. Column chromatography (DCM/MeOH/NH3) yields the title compound; [M+H]+=374;

Workup

  1. customthe cooling bath is removed
  2. additionAfter addition of saturated aqueous K2CO3 solution the layers
  3. customare separated
  4. concentrationthe aqueous layer is concentrated
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated

Sources & evidence

ORD record
ord-c9a8cbefcab64c00be4ca7cb20d3988a
Source dataset
uspto-grants-2012_11
Patent number
US08314112B2

Reaction notes

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