(1S,4S)-tert-butyl 2,5-diazabicyclo(2.2.1)heptane-2-carboxylate → 5-[6-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridine-3-carbonyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 627332Notes

Reaction equation

HRID 627332 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.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH:43]2[CH2:45][CH:40]1[CH2:41][NH:42]2)=[O:38])([CH3:35])([CH3:34])[CH3:33]>>[C:32]([O:36][C:37]([N:39]1[CH2:44][CH:43]2[CH2:45][CH:40]1[CH2:41][N:42]2[C:22]([C:21]1[CH:20]=[N:19][C:18]([NH:17][C:14]2[N:15]=[CH:16][C:11]3[CH:10]=[C:9]([C:27](=[O:31])[N:28]([CH3:29])[CH3:30])[N:8]([CH:1]4[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)[C:12]=3[N:13]=2)=[CH:26][CH:25]=1)=[O:24])=[O:38])([CH3:35])([CH3:33])[CH3:34]

Participants

3

Reactant 2

HCID 2760898(1S,4S)-tert-butyl 2,5-diazabicyclo(2.2.1)heptane-2-carboxylateHCID 673554046-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acid

Product 1

HCID 673545335-[6-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridine-3-carbonyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl esterYield 76%

Procedure

Following general amide formation method 1, 6-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acid (52.5 mg, 0.124 mmol, 1.0 eq) was combined with 2,5-Diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (32.0 mg, 0.162 mmol, 1.5 eq) which gave 5-[6-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridine-3-carbonyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (59 mg, 0.09 mmol, 76% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 9.12 (br s, 1H) 8.85 (s, 1H) 8.73 (br s, 1H) 8.61 (br s, 1H) 7.98 (br s, 1H) 6.48 (s, 1H) 4.47-4.65 (m, 2H) 3.72 (br s, 1H) 3.52-3.69 (m, 2H) 3.46 (t, J=8.59 Hz, 1H) 3.18 (s, 6H) 2.58-2.74 (m, 2H) 1.99-2.09 (m, 2H) 1.83-1.99 (m, 5H) 1.65-1.83 (m, 4H) 1.55-1.65 (m, 2H) 1.37-1.55 (m, 9H)

Sources & evidence

ORD record
ord-3da34ea473d744718d7ea748127f82f7
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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