Hydrochloric Acid → 6-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acid

HRID 1850532Notes

Reaction equation

HRID 1850532 reaction equation
C[O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:12]=[CH:13][C:14]3[CH:19]=[C:18]([C:20](=[O:24])[N:21]([CH3:23])[CH3:22])[N:17]([CH:25]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)[C:15]=3[N:16]=2)=[N:6][CH:5]=1.[Li+].[OH-].Cl>C1COCC1.O>[CH:25]1([N:17]2[C:15]3[N:16]=[C:11]([NH:10][C:7]4[CH:8]=[CH:9][C:4]([C:3]([OH:32])=[O:2])=[CH:5][N:6]=4)[N:12]=[CH:13][C:14]=3[CH:19]=[C:18]2[C:20](=[O:24])[N:21]([CH3:22])[CH3:23])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 673557986-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acid methyl ester

Product 1

HCID 673554046-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acidYield 37.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-(7-Cycloheptyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acid methyl ester (146 mg, 0.33 mmol, 1.0 eq) in THF (1.5 mL) was added LiOH (94.7 mg, 4.0 mmol, 12 eq) in 1.5 mL of water. The mixture was stirred at room temperature for 48 h. The reaction mixture was cooled to 0° C. in an ice bath and was acidified with 1N HCl until pH was about 1-2. The solid precipitate was filtered and washed to give the title compound as a light pink solid (52 mg, 0.124 mmol, 37%) and used as is; alternatively it can be extracted out with 20% Isopropanol in dichloromethane) 1H NMR (400 MHz, DMSO-d6) δ ppm 12.99 (br s, 1H) 10.38 (br s, 1H) 8.87 (s, 1H) 8.81 (d, J=2.01 Hz, 1H) 8.53 (d, J=9.03 Hz, 1H) 8.19 (dd, J=9.03, 2.01 Hz, 1H) 6.67 (s, 1H) 4.44 (br s, 1H) 3.07 (d, J=13.05 Hz, 6H) 2.54-2.60 (m, 2H) 1.87-1.98 (m, 2H) 1.75-1.87 (m, 2H) 1.59-1.75 (m, 4H) 1.49 (m, 2H). MS (m/z, MH+): 423.5

Workup

  1. temperatureThe reaction mixture was cooled to 0° C. in an ice bath
  2. filtrationThe solid precipitate was filtered
  3. washwashed

Sources & evidence

ORD record
ord-878c825d0073437c9d4305cd5929c1cf
Source dataset
uspto-grants-2015_02
Patent number
US08957074B2

Reaction notes

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