Dimethylformamide → 4-{6-Amino-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-3-yl}-3,6-dihydro-2H-pyridine-1-carboxamide

HRID 911959Notes

Reaction equation

HRID 911959 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]2[O:22][CH:21]=[C:20]([C:23]3[CH2:24][CH2:25][NH:26][CH2:27][CH:28]=3)[C:15]=2[CH:16]=[N:17][C:18]=1[NH2:19])[CH3:11].C[Si]([N:33]=[C:34]=[O:35])(C)C.CN(C=O)C.CCN(C(C)C)C(C)C>>[NH2:19][C:18]1[N:17]=[CH:16][C:15]2[C:20]([C:23]3[CH2:24][CH2:25][N:26]([C:34]([NH2:33])=[O:35])[CH2:27][CH:28]=3)=[CH:21][O:22][C:14]=2[C:13]=1[O:12][C@@H:10]([C:3]1[C:4]([Cl:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[Cl:1])[CH3:11]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 70696Trimethylsilyl isocyanateHCID 81531DiisopropylethylamineHCID 578124807-[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)furo[3,2-c]pyridin-6-ylamine

Product 1

HCID 441816544-{6-Amino-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-3-yl}-3,6-dihydro-2H-pyridine-1-carboxamide

Procedure

A mixture of 7-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)-furo[3,2-c]pyridin-6-ylamine (9.00 mg, 0.0213 mmol), trimethylsilyl isocyanate (5.31 μL, 0.0392 mmol), DMF (0.5 mL, 0.005 mol), and DIPEA (0.03 mL, 0.2 mmol) was stirred at rt for 3 h. The solution was taken directly for HPLC purification. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a yellow solid. 1H NMR (CD3OD, 400 MHz): δ=1.85-1.92 (m, 3H), 2.51 (br, s, 2H), 3.60-3.68 (m, 2H), 4.10 (br, s, 2H), 6.27 (d, J=3.5 Hz, 1H), 6.52 (q, J=6.8 Hz, 1H), 7.18-7.27 (m, 1H), 7.36-7.44 (m, 1H), 7.63-7.70 (m, 1H), 8.13-8.17 (m, 1H). MS (ES+): m/z 465.02 [MH+]. HPLC: tR=2.49 min (ZQ2, polar—5 min). The title compound was also converted to its mesylate and maleic acid salts by precipitation from ethanol.

Workup

  1. customThe solution was taken directly for HPLC purification
  2. additionThe fractions containing the pure product
  3. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-6a25226dc0ea4fecbcd0eafcb5fa5775
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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