Hydrazine hydrate (1:1) → HCID 118207806, compound

HRID 2205619Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[N:21]2[CH2:26][CH2:25][CH2:24][C@H:23]([N:27]3C(=O)C4C(=CC=CC=4)C3=O)[CH2:22]2)[CH3:10])[C:5]([C:38]#[N:39])=[C:4]([CH3:40])[N:3]=1.O.NN>C(O)C.C(#N)C>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[N:21]2[CH2:26][CH2:25][CH2:24][C@H:23]([NH2:27])[CH2:22]2)[CH3:10])[C:5]([C:38]#[N:39])=[C:4]([CH3:40])[N:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a 25 mL pear flask were added 2-amino-4-(((S)-1-(6-((S)-3-(1,3-dioxoisoindolin-2-yl)piperidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrile (20 mg, 0.037 mmol) and hydrazine monohydrate (0.081 mL, 1.7 mmol) in ethanol (1 mL). The mixture was heated to 65° C. for 4 hours. The mixture was diluted with acetonitrile and was then directly purified by preparative HPLC (basic mode, 25-45% ACN/water gradient). The product-containing fractions were combined and lyophilized to give the title compound as a light brown solid (6.9 mg, 46%). The absolute configuration of the stereocenter on the piperidine ring was not determined, but was assigned the opposite configuration of EXAMPLE 4. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50-1.56 (m, 3H), 1.84-1.96 (m, 1H), 2.01-2.12 (m, 2H), 2.14-2.26 (m, 2H), 2.31 (s, 4H), 2.57 (d, J=4.55 Hz, 2H), 2.89-2.99 (m, 1H), 3.43-3.51 (m, 1H), 3.59-3.67 (m, 1H), 3.78-3.85 (m, 3H), 6.27 (s, 1H), 6.53-6.56 (m, 1H), 7.43-7.47 (m, 1H), 7.88 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C21H27N9, 406. found 406.

Workup

customwas then directly purified by preparative HPLC (basic mode, 25-45% ACN/water gradient)

Sources & evidence

ORD record: ord-487aaf8631f0459f81772d8a15f74f36
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371321B2

Reaction notes

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