5-(Difluoromethoxy)picolinic acid → (E)-5-(Difluoromethoxy)-N-(8-(hydroxymethyl)-9-methyl-6,7-dihydro-5H-benzo[7]annulen-2-yl)picolinamide

HRID 1911046Notes

Reaction equation

HRID 1911046 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][CH2:9][C:8]([CH2:12][OH:13])=[C:7]([CH3:14])[C:6]=2[CH:15]=1.[F:16][CH:17]([F:28])[O:18][C:19]1[CH:20]=[CH:21][C:22]([C:25](O)=[O:26])=[N:23][CH:24]=1>>[F:28][CH:17]([F:16])[O:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][CH2:10][CH2:9][C:8]([CH2:12][OH:13])=[C:7]([CH3:14])[C:6]=3[CH:15]=2)=[O:26])=[N:23][CH:24]=1

Participants

3

Reactant 2

HCID 574758715-(Difluoromethoxy)picolinic acidHCID 86685427(2-amino-9-methyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methanol

Product 1

HCID 71060884(E)-5-(Difluoromethoxy)-N-(8-(hydroxymethyl)-9-methyl-6,7-dihydro-5H-benzo[7]annulen-2-yl)picolinamide

Procedure

In a manner similar to the procedure of step 3A, (E)-(2-amino-9-methyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methanol from preparation J was coupled with 5-(difluoromethoxy)picolinic acid from preparation K to afford the titled compound of step 46A. LCMS (M+H)+=375.27, 1H NMR (500 HMz, chloroform-d) δ 9.81 (s, 1H), 8.46 (d, J=2.1 Hz, 1H), 8.32 (dd, J=8.6, 0.5 Hz, 1H), 7.68-7.64 (m, 2H), 7.55 (dd, J=8.1, 2.3 Hz, 1H), 7.18 (d, J=8.1 Hz, 1H), 6.81-6.51 (m, 1H), 4.39 (s, 2H), 2.56-2.51 (m, 2H), 2.14 (s, 3H), 2.10 (quin, J=7.1 Hz, 2H), 2.00-1.96 (m, 2H), 1.89 (br. s., 1H).

Sources & evidence

ORD record
ord-bddcba3cd4734b728a637cf1ef9df736
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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