Triethylamine → Ethyl 6-chloro-7-(4-(6-(2,4-difluorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1626448Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[CH:33]=[CH:32][C:14]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:21][CH2:22][O:23]4)=[CH:18][C:17]=3[Cl:31])=[CH:13][CH:12]=2)=[O:10])[CH:5]=[CH:4][CH:3]=1.[F:34][C:35]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=1B(O)O.[F-].[Cs+].C(N(CC)CC)C>CC(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:31][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:16]=1[O:15][C:14]1[CH:32]=[CH:33][C:11]([C:9](=[O:10])[NH:8][C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([C:38]4[CH:37]=[CH:36][C:35]([F:34])=[CH:40][C:39]=4[F:41])[N:7]=3)=[CH:12][CH:13]=1)[O:23][CH2:22][CH2:21][CH:20]2[C:26]([O:28][CH2:29][CH3:30])=[O:27]

Participants

Conditions

Temperature: 105 °C

Procedure

Ethyl 7-(4-(6-bromopyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (Example 52, Step A, 40 mg, 0.0752 mmol), 2,4-difluorophenylboronic acid (15.4 mg, 0.0978 mmol), and cesium fluoride (29.7 mg, 0.196 mmol) in i-PrOH (1 ml) were sparged with argon for 2 minutes in a vial. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (3.09 mg, 0.00376 mmol) and triethylamine (15.7 μl, 0.113 mmol) were added and the vial capped. The reaction was heated to 105° C. for 90 minutes. The reaction was applied directly to a silica gel column and eluted with 20 to 80% ethyl acetate/hexanes gradient to provide the title compound (30 mg, 0.0531 mmol, 70.6% yield) as a white foam.

Workup

washeluted with 20 to 80% ethyl acetate/hexanes gradient

Sources & evidence

ORD record: ord-aef0e3fc4d1a47e4b184ae4f9e0baf02
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785445B2

Reaction notes

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