Trifluoroacetic acid → (S)-{4-[6-(3-Aminopiperidin-1-yl)pyridin-3-ylamino]-6-(3-chloro-5-fluoro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl}(cyclopropyl)methanone

HRID 526140Notes

Reaction equation

HRID 526140 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[N:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][C:14]([C:20]([CH:22]2[CH2:24][CH2:23]2)=[O:21])=[C:13]3[NH:25][C:26]2[CH:27]=[CH:28][C:29]([N:32]3[CH2:37][CH2:36][CH2:35][C@H:34]([NH:38]C(=O)OC(C)(C)C)[CH2:33]3)=[N:30][CH:31]=2)[CH:5]=[C:6]([F:9])[C:7]=1[OH:8].C(O)(C(F)(F)F)=O>>[NH2:38][C@H:34]1[CH2:35][CH2:36][CH2:37][N:32]([C:29]2[N:30]=[CH:31][C:26]([NH:25][C:13]3[C:12]4[C:17](=[CH:18][CH:19]=[C:10]([C:4]5[CH:5]=[C:6]([F:9])[C:7]([OH:8])=[C:2]([Cl:1])[CH:3]=5)[N:11]=4)[N:16]=[CH:15][C:14]=3[C:20]([CH:22]3[CH2:24][CH2:23]3)=[O:21])=[CH:27][CH:28]=2)[CH2:33]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136981870(S)-tert-Butyl 1-{5-[6-(3-chloro-5-fluoro-4-hydroxy-phenyl)-3-(cyclopropanecarbonyl)-1,5-naphthyridin-4-ylamino)pyridin-2-yl]piperidin-3-ylcarbamate

Product 1

HCID 136266674(S)-{4-[6-(3-Aminopiperidin-1-yl)pyridin-3-ylamino]-6-(3-chloro-5-fluoro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl}(cyclopropyl)methanoneYield 40%

Procedure

Following general procedure IV-2, (S)-tert-Butyl 1-{5-[6-(3-chloro-5-fluoro-4-hydroxy-phenyl)-3-(cyclopropanecarbonyl)-1,5-naphthyridin-4-ylamino)pyridin-2-yl]piperidin-3-ylcarbamate (100 mg, 0.16 mmol) was reacted with TFA (3 mL) to afford the desired product (33 mg, 40%) as an orange-red solid: 1H NMR (500 MHz, CD3OD) δ 9.15 (s, 1H), 8.06 (d, J=9.0 Hz, 1H), 8.01 (d, J=9.0 Hz, 1H), 7.94 (d, J=2.7 Hz, 1H), 7.40 (s, 1H), 7.33 (dd, J=9.0, 2.8 Hz, 1H), 6.94 (dd, J=12.6, 2.3 Hz, 1H), 6.69 (d, J=8.9 Hz, 1H), 4.20-4.10 (m, 1H), 3.87-3.77 (m, 1H), 3.30-3.21 (m, 1H), 3.13-3.03 (m, 2H), 2.91-2.83 (m, 1H), 2.17-2.06 (m, 1H), 1.90-1.82 (m, 1H), 1.77-1.51 (m, 2H), 1.43-1.04 (m, 4H); ESI MS m/z 533 [M+H]+; HPLC>99% (AUC), tR=9.97 min.

Sources & evidence

ORD record
ord-ce9866bed4134e8ca19f5caf2b82e132
Source dataset
uspto-grants-2016_05
Patent number
US09345709B2

Reaction notes

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