Ethyl chloroformate → 3-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridine-3-carbonyl]-3,8-diaza-bicyclo[3.2.1]octane-8-carboxylic acid ethyl ester

HRID 627387Notes

Reaction equation

HRID 627387 reaction equation
[CH3:1][N:2]([CH3:36])[C:3]([C:5]1[N:30]([CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([N:22]4[CH2:28][CH:27]5[NH:29][CH:24]([CH2:25][CH2:26]5)[CH2:23]4)=[O:21])=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].C(N(C(C)C)CC)(C)C.Cl[C:47]([O:49][CH2:50][CH3:51])=[O:48]>C(Cl)Cl.O>[CH2:50]([O:49][C:47]([N:29]1[CH:24]2[CH2:25][CH2:26][CH:27]1[CH2:28][N:22]([C:20]([C:17]1[CH:16]=[N:15][C:14]([NH:13][C:10]3[N:11]=[CH:12][C:7]4[CH:6]=[C:5]([C:3](=[O:4])[N:2]([CH3:36])[CH3:1])[N:30]([CH:31]5[CH2:35][CH2:34][CH2:33][CH2:32]5)[C:8]=4[N:9]=3)=[CH:19][CH:18]=1)=[O:21])[CH2:23]2)=[O:48])[CH3:51]

Participants

6

Reactant 3

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 533786742-(5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Product 1

HCID 866866453-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridine-3-carbonyl]-3,8-diaza-bicyclo[3.2.1]octane-8-carboxylic acid ethyl esterYield 21.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
23 °C

Procedure

To a solution of 7-cyclopentyl-2-[5-(3,8-diaza-bicyclo[3.2.1]octane-3-carbonyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (100 mg, 0.205 mmol, 1.0 eq) and Diisopropylethylamine (0.071 mL, 0.409 mmol, 2.0 eq) in CH2Cl2 (5 mL) was added Ethyl Chloroformate (0.022 mL, 0.225 mmol, 1.1 eq) diluted in 3.0 mL of CH2Cl2. The reaction mixture was stirred at 23° C. for 1 hour then diluted with water. The organic was collected and dried over Na2SO4, filtered, and concentrated. The crude reaction was purified using silica gel chromatography which gave 3-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridine-3-carbonyl]-3,8-diaza-bicyclo[3.2.1]octane-8-carboxylic acid ethyl ester (25 mg) in 21% yield. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.22-1.37 (m, 4H) 1.60 (br. s., 2H) 1.69-1.82 (m, 3H) 1.97 (br. s., 3H) 2.04-2.20 (m, 4H) 2.56 (d, J=8.59 Hz, 2H) 3.19 (s, 6H) 3.60 (br. s., 2H) 4.21 (q, J=7.07 Hz, 2H) 4.36 (br. s., 2H) 4.56 (br. s., 1H) 4.83 (t, J=8.59 Hz, 1H) 6.52 (s, 1H) 7.82 (dd, J=8.59, 2.02 Hz, 1H) 8.39 (d, J=2.02 Hz, 1H) 8.59 (d, J=8.59 Hz, 1H) 8.77 (s, 1H). HRMS m/z, (M+H)+: 561.2946.

Workup

  1. customThe organic was collected
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude reaction
  6. customwas purified

Sources & evidence

ORD record
ord-8681e60f18b8407b803d1824841432b6
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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