Lithium Chloride → (1R,5S)-tert-butyl 7-(6-(7-cycloheptyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinoyl)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate

HRID 627331Notes

Reaction equation

HRID 627331 reaction equation
[CH:1]1([N:8]2[C:12]3[N:13]=[C:14]([NH:17][C:18]4[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][N:19]=4)[N:15]=[CH:16][C:11]=3[CH:10]=[C:9]2[C:27](=[O:31])[N:28]([CH3:30])[CH3:29])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[Cl-].[OH:34][CH:35]1[C@H:40]2[CH2:41][NH:42][CH2:43][C@@H:36]1[CH2:37][N:38]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:39]2>>[CH:1]1([N:8]2[C:12]3[N:13]=[C:14]([NH:17][C:18]4[CH:26]=[CH:25][C:21]([C:22]([N:42]5[CH2:41][C@H:40]6[CH:35]([OH:34])[C@H:36]([CH2:37][N:38]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:39]6)[CH2:43]5)=[O:24])=[CH:20][N:19]=4)[N:15]=[CH:16][C:11]=3[CH:10]=[C:9]2[C:27](=[O:31])[N:28]([CH3:29])[CH3:30])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

4

Reactant 3

HCID 433294Lithium ChlorideHCID 673554046-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acidHCID 74787575(1R,5S)-tert-butyl 9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate

Product 1

HCID 67356145(1R,5S)-tert-butyl 7-(6-(7-cycloheptyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinoyl)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylateYield 83%

Procedure

Following general amide formation method 1, 6-(7-cycloheptyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid with 5 equiv LiCl was combined with (1R,5S)-tert-butyl 9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate which gave (1R,5S)-tert-butyl 7-(6-(7-cycloheptyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinoyl)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (170 mg) in 83% yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.75 (s, 1H), 8.67 (d, J=8.59 Hz, 1H), 8.42 (s, 1H), 8.31 (br s, 1H), 7.92 (d, J=8.08 Hz, 1H), 6.46 (s, 1H), 4.74-3.40 (m, 7H), 3.22-2.94 (m, 7H), 2.65 (m, 2H), 2.16-1.54 (m, 13H), 1.49 (s, 9H); LCMS m/z 647.1 (M+H)+.

Sources & evidence

ORD record
ord-1d4f8e530dfa498f9321a251db12f173
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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