1,1'-Carbonyldiimidazole → 5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-ylmethyl 2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate

HRID 1055158Notes

Reaction equation

[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[N:13]1[CH:14]=[CH:15][N:16]2[CH2:21][CH:20]([CH2:22][OH:23])[CH2:19][CH2:18][C:17]=12.O.Cl.Cl.[CH2:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29][CH:28]1[NH:36][C:37]1[N:38]=[CH:39][C:40]2[CH2:45][NH:44][CH2:43][C:41]=2[N:42]=1.C(N(C(C)C)CC)(C)C>ClCCl>[CH2:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:27][CH:28]1[NH:36][C:37]1[N:38]=[CH:39][C:40]2[CH2:45][N:44]([C:1]([O:23][CH2:22][CH:20]3[CH2:21][N:16]4[CH:15]=[CH:14][N:13]=[C:17]4[CH2:18][CH2:19]3)=[O:2])[CH2:43][C:41]=2[N:42]=1

Participants

Conditions

Temperature: 40 °C

Procedure

Add 1,1′-carbonyldiimidazole (2.87 g; 1.02 equiv; 17.69 mmoles) to a solution of 5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-ylmethanol (2.64 g; 1.00 equiv; 17.35 mmoles) in dichloromethane (30 mL), then stir at 40° C. for 1 hour. Add N-(2,3-dihydro-1H-inden-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-amine dihydrochloride hydrate (6.25 g; 1.05 equiv; 18.21 mmoles) and diisopropylethylamine (9.08 mL; 3.0 equiv; 52.04 mmoles) and maintain the reaction at 40° C. for 4 hours. Load the solution directly onto a diisopropylethylamine treated silica gel column and purify the mixture by column chromatography (0 to 15% methanol in ethyl acetate) to give 5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-ylmethyl 2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate (3.32 g; 44%) as a colorless foam. MS (m/z): 431(M+1).

Workup

customthe reaction at 40° C. for 4 hours
custompurify the mixture by column chromatography (0 to 15% methanol in ethyl acetate)

Sources & evidence

ORD record: ord-d01a100ef92346b78330288a074358e4
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394317B2

Reaction notes

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