Chloroacetyl chloride → 2-Chloro-1-[2-(indan-2-ylamino)-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl]ethanone

HRID 870569Notes

Reaction equation

O.Cl.Cl.[CH2:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH:5]1[NH:13][C:14]1[N:15]=[CH:16][C:17]2[CH2:22][NH:21][CH2:20][C:18]=2[N:19]=1.C(N(CC)CC)C.[Cl:30][CH2:31][C:32](Cl)=[O:33]>ClCCl>[Cl:30][CH2:31][C:32]([N:21]1[CH2:22][C:17]2[CH:16]=[N:15][C:14]([NH:13][CH:5]3[CH2:4][C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[CH2:6]3)=[N:19][C:18]=2[CH2:20]1)=[O:33]

Participants

Conditions

Temperature: -30 °C

Procedure

Stir a suspension of N-(2,3-dihydro-1H-inden-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-amine dihydrochloride hydrate (14.4 g, 41.9 mmol) and triethylamine (14.3 g, 19.7 mL, 141.4 mmol) in dichloromethane (200 mL) at 23° C. for 10 minutes, then cool to −30° C. Add 2-chloroacetyl chloride (5.49 g, 3.86 mL, 48.6 mmol) over two minutes and warm to 23° C. over 10 minutes. Add methanol (5 mL) and remove the solvent in vacuo. Slurry the crude reaction mixture in methanol (30 mL), add 50 g silica gel and remove solvent in vacuo. Load the resulting residue onto a loading column and purify via silica gel column chromatography (gradient elution: 50% ethyl acetate in hexanes to ethyl acetate to 10% methanol in ethyl acetate) to give the title compound (11.5 g, 84%). MS (m/z): 329(M+1).

Workup

temperaturewarm to 23° C. over 10 minutes
customAdd methanol (5 mL) and remove the solvent in vacuo
customreaction mixture in methanol (30 mL)
additionadd 50 g silica gel
customremove solvent in vacuo
customLoad the resulting residue onto a loading column and purify via silica gel column chromatography (gradient elution: 50% ethyl acetate in hexanes to ethyl acetate to 10% methanol in ethyl acetate)

Sources & evidence

ORD record: ord-eb1a22a742ca4fc3badd7e520190db8b
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969555B2

Reaction notes

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