(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate → Methyl(2S)-2-(tert-butoxy)-2-[2-(3-{4,5-difluoro-2-[(2S)-pent-4-en-2-yloxy]phenyl}phenyl)-7-methyl-5-[4-methyl-4-(prop-2-en-1-yloxy)piperidin-1-yl]imidazo[1,2-a]pyridin-6-yl]acetate

HRID 1482016Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5](B(O)O)=[C:4]([O:12][C@H:13]([CH2:15][CH:16]=[CH2:17])[CH3:14])[CH:3]=1.[CH2:18]([O:21][C:22]1([CH3:55])[CH2:27][CH2:26][N:25]([C:28]2[N:33]3[CH:34]=[C:35]([C:37]4[CH:42]=[CH:41][CH:40]=[C:39](Br)[CH:38]=4)[N:36]=[C:32]3[CH:31]=[C:30]([CH3:44])[C:29]=2[C@H:45]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])[C:46]([O:48][CH3:49])=[O:47])[CH2:24][CH2:23]1)[CH:19]=[CH2:20].C(OC1(C)CCN(C2N3C=C(C4C=C(C5C=CC(F)=CC=5O[C@H](CC=C)C)C=CC=4)N=C3C=C(C)C=2[C@H](OC(C)(C)C)C(OC)=O)CC1)C=C>>[C:51]([O:50][C@@H:45]([C:29]1[C:30]([CH3:44])=[CH:31][C:32]2[N:33]([CH:34]=[C:35]([C:37]3[CH:38]=[CH:39][CH:40]=[C:41]([C:5]4[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=4[O:12][C@H:13]([CH2:15][CH:16]=[CH2:17])[CH3:14])[CH:42]=3)[N:36]=2)[C:28]=1[N:25]1[CH2:24][CH2:23][C:22]([CH3:55])([O:21][CH2:18][CH:19]=[CH2:20])[CH2:27][CH2:26]1)[C:46]([O:48][CH3:49])=[O:47])([CH3:52])([CH3:53])[CH3:54]

Participants

Reactant 3

HCID 118308811(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

HCID 118308907(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4'-fluoro-2'-((S)-pent-4-en-2-yloxy)-[1,1'-biphenyl]-3-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

HCID 123993303(S)-(4,5-Difluoro-2-(pent-4-en-2-yloxy)phenyl)boronic acid

Product 1

HCID 118308878Methyl(2S)-2-(tert-butoxy)-2-[2-(3-{4,5-difluoro-2-[(2S)-pent-4-en-2-yloxy]phenyl}phenyl)-7-methyl-5-[4-methyl-4-(prop-2-en-1-yloxy)piperidin-1-yl]imidazo[1,2-a]pyridin-6-yl]acetateYield 72%

Procedure

Prepared in 72% yield from (S)-(4,5-difluoro-2-(pent-4-en-2-yloxy)phenyl)boronic acid and (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate following the procedure for (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4′-fluoro-2′-((S)-pent-4-en-2-yloxy)-[1,1′-biphenyl]-3-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate. 1H NMR (400 MHz, CDCl3) δ 8.07-7.88 (m, 3H), 7.51-7.38 (m, 3H), 7.32 (br. s., 1H), 6.92-6.74 (m, 1H), 6.14-6.00 (m, 2H), 5.80-5.65 (m, 1H), 5.51-5.40 (m, 1H), 5.12-4.97 (m, 3H), 4.28-4.17 (m, 1H), 4.05-3.95 (m, 3H), 3.86-3.77 (m, 1H), 3.69 (s, 3H), 3.07-2.97 (m, 1H), 2.79-2.65 (m, 1H), 2.47 (s, 3H), 2.41-2.30 (m, 1H), 2.29-2.18 (m, 1H), 2.04-1.92 (m, 2H), 1.88-1.68 (m, 2H), 1.33 (s, 3H), 1.27 (s, 9H), 1.19 (d, J=6.0 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −137.17-−137.33 (d, J=23 Hz, 1F), −147.78-−147.92 (d, J=23 Hz, 1F); LCMS (ESI, M+1): 702.25.

Sources & evidence

ORD record: ord-933dc8e096bc4bbdac3a8fb6be48e711
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409922B2

Reaction notes

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