Trifluoroacetic acid → HCID 136338256, compound

HRID 1529440Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13](C2CCCCO2)[N:12]=[C:11]3[C:23]2[CH:28]=[C:27]([O:29]CC3C=CC(OCC)=CC=3)[N:26]=[C:25]([O:40][C@H:41]3[C@H:46]([F:47])[CH2:45][CH2:44][N:43](C(OCC4C=CC=CC=4)=O)[CH2:42]3)[N:24]=2)=[C:4]([F:58])[CH:3]=1.[C:59]([OH:65])([C:61]([F:64])([F:63])[F:62])=[O:60]>>[F:62][C:61]([F:64])([F:63])[C:59]([OH:65])=[O:60].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13][N:12]=[C:11]3[C:23]2[N:24]=[C:25]([O:40][C@H:41]3[C@H:46]([F:47])[CH2:45][CH2:44][NH:43][CH2:42]3)[NH:26][C:27](=[O:29])[CH:28]=2)=[C:4]([F:58])[CH:3]=1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 67960691HCID 67960691, compound

Product 1

HCID 136338256HCID 136338256, compoundYield 21%

Conditions

Temperature: 100 °C

Procedure

A glass microwave reaction vessel was charged with benzyl 3-((4-(5-(4-chloro-2-fluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-6-((4-ethoxybenzyl)oxy)pyrimidin-2-yl)oxy)-(trans)-4-fluoropiperidine-1-carboxylate (200 mg, 0.25 mmol) and TFA (1 mL). The reaction was stirred and heated in a microwave reactor at 100° C. for 30 min. The solvent was removed in vacuo and the residue was purified with preparative HPLC (eluting with 20-100% MeCN in water with 0.1% TFA) to give 6-(5-(4-chloro-2-fluorophenyl)-1H-indazol-3-yl)-2-((trans-4-fluoropiperidin-3-yl)oxy)pyrimidin-4(3H)-one trifluoroacetate (racemic) (30 mg, 21%) as a off white solid. MS (ESI, pos. ion) m/z: 458.3 (M+1); 1H NMR (400 MHz, DMSO-d6): δ ppm 13.81 (s, 1H), 8.82 (bs, 1H), 8.55 (s, 1H), 7.76 (d, 1 H, J=8.8 Hz), 7.62-7.67 (m, 2H), 7.58 (dd, 1 H, J=8.8, 2 Hz), 7.43 (dd, 1 H, J=6.4, 1.6 Hz), 5.64 (s, 1H), 5.24 (s, 1H), 3.41-3.49 (m, 2H), 3.13-3.20 (m, 2H), 2.18-2.32 (m, 1H), 1.95-2.05 (m, 1H).

Workup

customA glass microwave reaction vessel
customThe solvent was removed in vacuo
customthe residue was purified with preparative HPLC (eluting with 20-100% MeCN in water with 0.1% TFA)

Sources & evidence

ORD record: ord-ae79a198879f4e7eaebc7dc239b1a753
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

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