Hydrochloric Acid → 2-(7-(Dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-5-methylthiazole-4-carboxylic acid

HRID 220381Notes

Reaction equation

[OH-].[Na+].[CH:3]1([N:6]([CH:35]2[CH2:37][CH2:36]2)[C:7]([C:9]2[N:32]([CH2:33][CH3:34])[C:12]3=[N:13][C:14]([NH:21][C:22]4[S:23][C:24]([CH3:31])=[C:25]([C:27]([O:29]C)=[O:28])[N:26]=4)=[C:15]4[N:19]=[CH:18][N:17]([CH3:20])[C:16]4=[C:11]3[CH:10]=2)=[O:8])[CH2:5][CH2:4]1.Cl>C(O)C>[CH:35]1([N:6]([CH:3]2[CH2:4][CH2:5]2)[C:7]([C:9]2[N:32]([CH2:33][CH3:34])[C:12]3=[N:13][C:14]([NH:21][C:22]4[S:23][C:24]([CH3:31])=[C:25]([C:27]([OH:29])=[O:28])[N:26]=4)=[C:15]4[N:19]=[CH:18][N:17]([CH3:20])[C:16]4=[C:11]3[CH:10]=2)=[O:8])[CH2:36][CH2:37]1

Participants

Conditions

Temperature: 60 °C

Procedure

1N Aqueous NaOH (0.962 mL, 0.962 mmol) was added to a suspension of methyl 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-5-methylthiazole-4-carboxylate (example 41, 0.19 g, 0.385 mmol) in ethanol (2 mL) and the mixture was heated at 60° C. for 2 h. The reaction was cooled to room temperature and acidified with 1N HCl to pH 4. The reaction mixture was concentrated and the residue triturated 5× with methanol. The combined methanol washes were concentrated, and the remaining solid washed 3× with 2:1 ether/dichloromethane provided 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-5-methylthiazole-4-carboxylic acid (105 mg, 57% yield).

Workup

temperatureThe reaction was cooled to room temperature
concentrationThe reaction mixture was concentrated
customthe residue triturated 5× with methanol
concentrationThe combined methanol washes were concentrated
washthe remaining solid washed 3× with 2:1 ether/dichloromethane

Sources & evidence

ORD record: ord-a18591cef86d4791a563a8fc3b074f1c
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202881B2

Reaction notes

Loading…