3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole → HCID 178480085, compound

HRID 1947008Notes

Reaction equation

[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]1.Cl[C:10]1[N:15]=[C:14]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH3:25])[CH:17]=2)[CH:13]=[CH:12][N:11]=1>CN1C(=O)CCC1>[CH3:25][N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16]([C:14]2[CH:13]=[CH:12][N:11]=[C:10]([NH:1][C@H:2]3[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]3)[N:15]=2)=[CH:17]1

Participants

Conditions

Temperature: 120 °C

Procedure

trans-4-Aminocyclohexanol (0.45 g, 4 mmol) was added to 3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole (0.23 g, 1 mmol) in NMP (8 mL), and the resulting mixture heated to 120° C. for 3 h. A second aliquot of trans-4-aminocyclohexanol (0.16 g, 1 mmol) was added, and the resulting mixture was heated to 130° C. The reaction mixture was cooled and partitioned between water and EtOAc, the organic layer separated, washed twice with water, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was recrystallized from DCM/EtOAc/hexanes to give trans-4-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-cyclo-hexanol (148 mg, 46% yield) as a light-yellow solid. MS=323 [M+H]+; MP=194.5-195.3° C.

Workup

temperaturethe resulting mixture was heated to 130° C
temperatureThe reaction mixture was cooled
custompartitioned between water and EtOAc
customthe organic layer separated
washwashed twice with water
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude residue was recrystallized from DCM/EtOAc/hexanes

Sources & evidence

ORD record: ord-6fb74bd5996547abba637a5ff7365cb8
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399462B2

Reaction notes

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