Guanidine Hydrochloride → Pik-iii

HRID 2359750Notes

Reaction equation

[CH:1]1([CH2:4][C:5](=O)/[C:6](/[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[N:12]=2)=[CH:7]\N(C)C)[CH2:3][CH2:2]1.Cl.[NH2:26][C:27]([NH2:29])=[NH:28].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH:1]1([CH2:4][C:5]2[C:6]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[N:12]=3)=[CH:7][N:26]=[C:27]([NH2:29])[N:28]=2)[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (3Z)-1-cyclopropyl-4-(dimethylamino)-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]but-3-en-2-one (9) (80 mg, 0.247 mmol) in DMF (2061 μl), Guanidine HCl (35.3 mg, 0.371 mmol) and potassium carbonate (103 mg, 0.742 mmol) were added and the reaction was heated at 60° C. for 4 hours. The crude product was purified by reverse-phase HPLC [30-90% organic phase over 15 minutes] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 12% MeOH/DCM] to obtain the desired product as a white solid (24.72 mg, 31.3% yield). 1H NMR (400 MHz, MeOD) δ ppm 0.01-0.14 (m, 2H) 0.39 (q, J=6.06 Hz, 2H) 0.94-1.10 (m, 1H) 2.87 (d, J=7.07 Hz, 2H) 7.10 (d, J=5.05 Hz, 1H) 7.83 (d, J=6.57 Hz, 2H) 8.30 (d, J=6.57 Hz, 2H) 8.41 (s, 1H) 8.57 (d, J=5.05 Hz, 1H). HRMS (ES+) for C17H17N7.H+ [MH+]: calcd, 320.1624; found, 320.1636. UV-LC: 100% UV purity at 254/214 nm; tR=4.67 minute over 7.75 minutes.

Workup

customThe crude product was purified by reverse-phase HPLC [30-90% organic phase over 15 minutes]

Sources & evidence

ORD record: ord-1b5bc340cf864feb89e755b572440015
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08685993B2

Reaction notes

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