Methanol → Alectinib

HRID 61876Notes

Reaction equation

[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:35](O)=[O:36])=[C:8]([C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH3:22])=[C:17]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:25][CH2:24]4)[CH:16]=3)([CH3:14])[CH3:13])[NH:9]2)=[CH:5][CH:4]=1)#[N:2].CO.O>CC(N(C)C)=O.C(OC(=O)C)(=O)C.CCN(C(C)C)C(C)C>[CH2:21]([C:18]1[C:17]([N:23]2[CH2:24][CH2:25][CH:26]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[CH2:27][CH2:28]2)=[CH:16][C:15]2[C:12]([CH3:14])([CH3:13])[C:8]3[NH:9][C:10]4[C:6]([C:7]=3[C:35](=[O:36])[C:20]=2[CH:19]=1)=[CH:5][CH:4]=[C:3]([C:1]#[N:2])[CH:11]=4)[CH3:22]

Participants

Conditions

Temperature: 90 °C

Procedure

6-Cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid (500 g) was dissolved in a mixture of DMA (9.4 L), acetic anhydride (270 ml) and DIPEA (1170 ml) under nitrogen stream. The mixture was stirred at 90° C. for 1 hr. After cooling to room temperature, the mixture was added with methanol (3.525 L) and subsequently with distilled water (5.875 L). The precipitated solid was filtered, collected, washed twice with the mixture solution (methanol:water=3:5, 1.41 L), and then dried to obtain the title compound (389.6 g, 85%).

Workup

temperatureAfter cooling to room temperature
filtrationThe precipitated solid was filtered
customcollected
washwashed twice with the mixture solution (methanol:water=3:5, 1.41 L)
customdried

Sources & evidence

ORD record: ord-db92dd1528e74322a0f7be4b9c2e98ce
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440922B2

Reaction notes

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