Methanol → 1-[5-(4-Amino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-(2,3-difluoro-phenyl)-ethanone

HRID 269510Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10](Cl)=[O:11].C(OC(=O)[NH:19][CH:20]1[CH2:25][CH2:24][CH:23]([C:26]2[CH:31]=[CH:30][C:29]3[NH:32][CH:33]=[CH:34]C=3N=2)[CH2:22][CH2:21]1)(C)(C)C.[Al+3].[Cl-].[Cl-].[Cl-].CO.ClC1C(Cl)=CC=CC=1C1[CH:51]=[N:52]OC=1C1C2C(=NC=CC=2)NC=1>C(Cl)Cl>[NH2:19][CH:20]1[CH2:21][CH2:22][CH:23]([C:26]2[CH:31]=[C:30]3[C:34]([C:10](=[O:11])[CH2:9][C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=4[F:1])=[CH:33][NH:32][C:29]3=[N:52][CH:51]=2)[CH2:24][CH2:25]1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 2,3-difluorophenylacetyl chloride (1.0 mmol) in CH2Cl 2(3 ml) was added dropwise to a mixture of [4-(1H-pyrrolo[2,3-]pyridin-5-yl)-cyclohexyl]-carbamic acid tert-butyl ester (280 mg, 0.88 mmol) and AlCl3 (612 mg, 4.6 mmol) in CH2Cl2(15 ml) at 0° C. After the addition, the reaction was stirred for 1.5 hrs at 0° C. Methanol (5 ml) was added to the reaction. After 1 hr. the reaction was evaporated and the resulting residue purified by flash chromatography to afford 1-[5-(4-Amino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl ]-2-(2,3-difluoro-phenyl)-ethanone (229 mg) in 70.5% yield. LC-MS: m/e=370.3 (M+H), 368.4 (M−H). After the treatment of the above cyclohexylamine (220 mg, 0.60 mmol) with 37% formaldehyde (2 ml) and formic acid (4 ml) at 80° C. for 15 h, pure 2-(2,3-Difluoro-phenyl)-1-[5-(4-dimethylamino-cyclohexyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone was obtained by FC (167 mg) in 70.1% yield. LC-MS: m/e: 398.4 (M+H), 396.4 (M−H).

Workup

additionAfter the addition
waitAfter 1 hr
customthe reaction was evaporated
customthe resulting residue purified by flash chromatography

Sources & evidence

ORD record: ord-b39d435243254c0abfa1d0ad5841fa83
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07446199B2

Reaction notes

Loading…