Hydrochloric Acid → (1S,3R)-N1-(2-fluoro-5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)cyclohexane-1,3-diamine

HRID 526990Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)=[CH:4][C:3]=1[NH:28][C@H:29]1[CH2:34][CH2:33][CH2:32][C@@H:31]([NH:35]C(=O)OC(C)(C)C)[CH2:30]1.FC1C(N[C@H]2CCC[C@@H](NC(=O)OC(C)(C)C)C2)=NC(C2C3C(=NC=C(F)C=3)N(S(C3C=CC(C)=CC=3)(=O)=O)C=2)=NC=1.Cl>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][CH:9]=2)=[CH:4][C:3]=1[NH:28][C@H:29]1[CH2:34][CH2:33][CH2:32][C@@H:31]([NH2:35])[CH2:30]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of tert-butyl (1R,3S)-3-(2-fluoro-5-(5-fluoro-1-tosyl-1H-pyrrolo-[2,3-b]pyridin-3-yl)phenylamino)cyclohexylcarbamate, 44d, (0.65 g, 1.09 mmol) in methylene chloride (22 mL) was added hydrogen chloride (2.71 mL of 4M solution in 1,4-dioxane, 10.86 mmol). The reaction was heated to 50° C. and stirred for 6 hours. The mixture was cooled to room temperature and concentrated in vacuo, producing a yellow solid. The crude residue was purified via silica gel chromatography (25-50% Ethyl Acetate/hexanes gradient). Desired fractions were combined and concentrated in vacuo to produce 350 mg of 44e as a yellow powder.

Workup

temperatureThe mixture was cooled to room temperature
concentrationconcentrated in vacuo
customproducing a yellow solid
customThe crude residue was purified via silica gel chromatography (25-50% Ethyl Acetate/hexanes gradient)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-6acd43f0fdaf4336b9df361d2dd71827
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345708B2

Reaction notes

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