Ethyl Acetate → 4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)aniline

HRID 77706Notes

Reaction equation

FC1C=C(C=CC=1)C([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19]2[N:24]=[CH:25][N:26]=[CH:27][C:18]3=2)[CH:9]=1)=O.O1CCOCC1.[OH-].[Na+].CCOC(C)=O>CC(O)C.C(Cl)(Cl)Cl>[CH3:14][C:11]1[CH:12]=[CH:13][C:8]([NH2:7])=[CH:9][C:10]=1[C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][C:19]1[N:24]=[CH:25][N:26]=[CH:27][C:18]2=1

Participants

Conditions

Temperature: 100 °C

Procedure

To 3-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]benzamide (205 mg, 0.517 mmol) was added 1,4-dioxane (3.1 mL) and aqueous sodium hydroxide (3.8M, 2.72 mL, 10.0 mmol) followed by solid sodium hydroxide (1.67 g, 41.7 mmol). The reaction was heated to 100° C. until LCMS indicated complete hydrolysis, typically 16-24 hours. The reaction was cooled to ambient temperature and partitioned between water and EtOAc, which resulted in the formation of solids. These solids were dissolved through successive extractions with EtOAc and 3:1 CHCl3:IPA. The organic phases were separately washed with water and saturated aqueous NaCl, then dried (MgSO4), the dried solutions were combined and evaporated to dryness to leave the crude product (133 mg, 93.8%). 1H NMR (300 MHz, DMSO): δ 12.33 (bs, 1H), 9.46 (s, 1H), 8.91 (s, 1H), 8.16 (s, 1H), 7.57 (d, 1H), 7.44 (dd, 1H), 6.94 (d, 1H), 6.4-6.6 (m, 2H), 5.00 bs, 2H), 2.08 (s, 3H). MS (EI) m/z=275 (M+H).

Workup

customhydrolysis, typically 16-24 hours
temperatureThe reaction was cooled to ambient temperature
custompartitioned between water and EtOAc, which
customresulted in the formation of solids
washThe organic phases were separately washed with water and saturated aqueous NaCl
dry with materialdried (MgSO4)
customevaporated to dryness

Sources & evidence

ORD record: ord-ee69d0c62f934358b50f318d2ffcb93c
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841318B2

Reaction notes

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