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

HRID 627330Notes

Reaction equation

HRID 627330 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:25](=[O:29])[N:26]([CH3:28])[CH3:27])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[Cl-].[OH:32][CH:33]1[C@H:38]2[CH2:39][NH:40][CH2:41][C@@H:34]1[CH2:35][N:36]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37]2>>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:24]=[CH:23][C:19]([C:20]([N:40]5[CH2:39][C@H:38]6[CH:33]([OH:32])[C@H:34]([CH2:35][N:36]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37]6)[CH2:41]5)=[O:21])=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:25](=[O:29])[N:26]([CH3:27])[CH3:28])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 3

HCID 433294Lithium ChlorideHCID 583154726-(7-cyclopentyl-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 67379554(1R,5S)-tert-butyl 7-(6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinoyl)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylateYield 77%

Procedure

Following general amide formation method 1, 6-(7-cyclopentyl-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-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinoyl)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (158 mg) in 77% yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.76 (s, 1H), 8.56 (d, J=8.59 Hz, 1H), 8.41 (s, 1H), 8.28 (br s, 1H), 7.92 (d, J=7.07 Hz, 1H), 6.47 (s, 1H), 4.80 (m, 1H), 4.67-4.29 (m, 2H), 4.14-3.68 (m, 3H), 3.48 (m, 1H), 3.24-2.99 (m, 7H), 2.60 (m, 2H), 2.26-1.54 (m, 10H), 1.49 (s, 9H); LCMS m/z 619.0 (M+H)+.

Sources & evidence

ORD record
ord-2cec080d0f7c4127a1aaa0ccf5b437c3
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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