5H,7H,8H-pyrano[4,3-b]pyridin-3-amine → (R)-6-Trifluoromethyl-2,3-dihydro-benzo[1,4]dioxine-2-carboxylic acid (7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-yl)-amide

HRID 1697473Notes

Reaction equation

HRID 1697473 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:15]=[CH:14][C:6]2[O:7][C@@H:8]([C:11]([OH:13])=O)[CH2:9][O:10][C:5]=2[CH:4]=1.[N:18]1[CH:23]=[C:22]([NH2:24])[CH:21]=[C:20]2[CH2:25][O:26][CH2:27][CH2:28][C:19]=12>>[N:18]1[CH:23]=[C:22]([NH:24][C:11]([C@@H:8]2[O:7][C:6]3[CH:14]=[CH:15][C:3]([C:2]([F:1])([F:17])[F:16])=[CH:4][C:5]=3[O:10][CH2:9]2)=[O:13])[CH:21]=[C:20]2[CH2:25][O:26][CH2:27][CH2:28][C:19]=12

Participants

3

Reactant 2

HCID 107969175H,7H,8H-pyrano[4,3-b]pyridin-3-amineHCID 58125504(R)-6-trifluoromethyl-2,3-dihydrobenzo[1,4]dioxine-2-carboxylic acid

Product 1

HCID 44194670(R)-6-Trifluoromethyl-2,3-dihydro-benzo[1,4]dioxine-2-carboxylic acid (7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-yl)-amideYield 91.2%

Procedure

The compound is prepared in a similar manner as Compound 18 by condensing (R)-6-(trifluoromethyl)-2,3-dihydrobenzo[1,4]dioxine-2-carboxylic acid (38 mg, 0.15 mmol) with 7,8-dihydro-5H-pyrano[4,3-b]pyridin-3-ylamine (42 mg, 0.28 mmol) for 16 hours and purified by semi-preparative HPLC (55-75 gradient) to give the titled amide (52 mg, 89%). m/z=381.1 (M+1)4. HPLC: 9.62 min. 1H NMR (400 MHz; d6-DMSO) δ 10.38 (m, 1H), 8.52 (d, 1H, J=2.3 Hz), 7.77 (d, 1H, J=2.3 Hz), 7.36 (d, 1H, J=2.0 Hz), 7.26-7.22 (m, 2H), 7.09 (d, 1H, J=7.7 Hz), 5.17-5.14 (m, 1H), 4.52-4.49 (m, 2H), 3.95 (t, 2H, J=5.7 Hz), 2.82 (t, 211, J=5.7 Hz).

Workup

  1. customThe compound is prepared in a similar manner as Compound 18
  2. custompurified by semi-preparative HPLC (55-75 gradient)

Sources & evidence

ORD record
ord-a994226e99ad4137a32a924bfb91e793
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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