1-[4-(4-{6-Amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidin-1-yl]-2-hydroxy-ethanone → Crizotinib

HRID 2266717Notes

Reaction equation

ClC1C(F)=CC=C(Cl)C=1[C@H](OC1C(N)=NC=C(B2OC(C)(C)C(C)(C)O2)C=1)C.[NH2:29][C:30]1[N:35]=[CH:34][C:33]([C:36]2[CH:37]=[N:38][N:39]([CH:41]3[CH2:46][CH2:45][N:44](C(=O)CO)[CH2:43][CH2:42]3)[CH:40]=2)=[CH:32][C:31]=1[O:51][C@@H:52]([C:54]1[C:59]([Cl:60])=[CH:58][CH:57]=[C:56]([F:61])[C:55]=1[Cl:62])[CH3:53]>>[Cl:62][C:55]1[C:56]([F:61])=[CH:57][CH:58]=[C:59]([Cl:60])[C:54]=1[C@H:52]([O:51][C:31]1[C:30]([NH2:29])=[N:35][CH:34]=[C:33]([C:36]2[CH:37]=[N:38][N:39]([CH:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)[CH:40]=2)[CH:32]=1)[CH3:53]

Participants

Reactant 2

HCID 116131271-[4-(4-{6-Amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidin-1-yl]-2-hydroxy-ethanone

HCID 59599412(R)-3-(1-(2,6-Dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

Product 1

HCID 11626560Crizotinib

Procedure

The title compound was prepared according to procedure 62 using 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine and 4-(4-bromo-pyrazol-1-yl)-1-cyclopentyl-piperidine (prepared according to general procedure 11 using bromocyclopentane as alkylation reagent). 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.55 (s, 1H), 7.48 (s, 1H), 7.31 (m, 1H), 7.07 (m, 1H), 6.88 (s, 1H), 6.08 (m, 1H), 4.64 (m, 1H), 2.04 (m, 2H), 1.98 (m, 2H), 1.86 (d, J=8 Hz, 3H), 1.73 (m, 2H); LCMS: 435 [M+1]; c-Met Ki: 0.02 μM.

Sources & evidence

ORD record: ord-146753013eab416a98bbe63a7e867da0
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858643B2

Reaction notes

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