N,N-Dimethylpiperidin-4-amine → 1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-N,N-dimethylpiperidin-4-amine

HRID 1692878Notes

Reaction equation

HRID 1692878 reaction equation
[CH3:1][N:2]([CH3:9])[CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.Br[CH2:11][C:12]1[N:13]([CH3:28])[C:14]2[C:19]([N:20]=1)=[C:18]([N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)[N:17]=[C:16]([Cl:27])[N:15]=2>>[Cl:27][C:16]1[N:15]=[C:14]2[C:19]([N:20]=[C:12]([CH2:11][N:6]3[CH2:7][CH2:8][CH:3]([N:2]([CH3:9])[CH3:1])[CH2:4][CH2:5]3)[N:13]2[CH3:28])=[C:18]([N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)[N:17]=1

Participants

3

Reactant 2

HCID 417391N,N-Dimethylpiperidin-4-amineHCID 596034814-(8-(bromomethyl)-2-chloro-9-methyl-9H-purin-6-yl)morpholine

Product 1

HCID 596035251-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-N,N-dimethylpiperidin-4-amineYield 45.8%

Procedure

N,N-dimethylpiperidin-4-amine (0.41 g) was reacted with 4-(8-(bromomethyl)-2-chloro-9-methyl-9H-purin-6-yl)morpholine (1.0 g) via General Procedure C to yield 1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-N,N-dimethylpiperidin-4-amine (0.52 g) as a white solid. This intermediate was reacted with 1-(phenylsulfonyl)-1H-indol-3-ylboronic acid via General Procedure B to give intermediate N,N-dimethyl-1-((9-methyl-6-morpholino-2-(1-(phenylsulfonyl)-1H-indol-3-yl)-9H-purin-8-yl)methyl)piperidin-4-amine. The intermediate was suspended in MeOH (3 mL) whereupon 3N KOH (0.3 mL) was added and the reaction mixture was heated at 50° C. for several hours until the protecting group was removed. Reverse phase purification gave 110. MS (Q1) 475.3 (M)+. 1H NMR (400 MHz, DMSO) δ 11.46 (s, 1H), 8.66-8.51 (m, 1H), 8.13 (d, 1H), 7.48-7.36 (m, 1H), 7.19-7.08 (m, 2H), 4.26 (s, 4H), 3.93 (d, 3H), 3.83-3.75 (m, 4H), 3.70 (s, 2H), 2.84 (d, 2H), 2.15 (s, 6H), 2.11-1.94 (m, 3H), 1.72 (d, 2H), 1.36 (q, 2H)

Sources & evidence

ORD record
ord-ad11d99af4344af980e943ea1f1f6433
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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