Glycolic Acid → 1-[4-{6-Amino-7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-3-yl}-3,6-dihydropyridin-1(2H)-yl]-2-hydroxyethanone

HRID 911968Notes

Reaction equation

HRID 911968 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].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:60](O)(=[O:63])[CH2:61][OH:62]>C(Cl)Cl>[NH2:19][C:18]1[N:17]=[CH:16][C:15]2[C:20]([C:23]3[CH2:24][CH2:25][N:26]([C:61](=[O:62])[CH2:60][OH:63])[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

6

Reactant 4

HCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57812480HCID 57812480, compound

Product 1

HCID 578126771-[4-{6-Amino-7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-3-yl}-3,6-dihydropyridin-1(2H)-yl]-2-hydroxyethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 7-[(R)-1-(2,6-Dichloro-3-fluorophenyl)-ethoxy]-3-(1,2,3,6-tetrahydro-pyridin-4-yl)-furo[3,2-c]pyridin-6-ylamine (0.010 g, 0.024 mmol), DIPEA (0.00918 g, 0.071 mmol), TBTU (0.0228 g, 0.071 mmol) in DCM (2 mL) was added Glycolic acid (0.00360 g, 0.0474 mmol) at 0° C. The mixture was stirred for 1 h. The reaction mixture was directly loaded onto Prep TLC for purification (silica gel, eluting with 4% MeOH in DCM) to afford the title compound as a yellow solid. 1H-NMR (CD3OD, 400 MHz): δ=1.88 (d, J=6.8 Hz, 3H), 2.53 (d, J=17.2 Hz, 2H), 3.63 (t, J=5.8 Hz, 1H), 3.83 (t, J=5.8 Hz, 1H), 4.12 (d, J=2.0 Hz, 1H), 4.26 (s, 2H), 4.30 (s, 1H), 6.29 (d, 1H), 6.49 (q, J=6.7 Hz, 1H), 7.15-7.25 (m, 1H), 7.39 (dd, J=9.0, 4.9 Hz, 1H), 7.64 (d, J=10.4 Hz, 1H), 8.20 (s, 1H). MS (ES+): m/z 480.01 (MH+, 35Cl, 37Cl), 481.96 (MH+, 37Cl, 37Cl). HPLC: tR=2.76 min (polar—5 min, ZQ3).

Workup

  1. customThe reaction mixture was directly loaded onto Prep TLC for purification (silica gel, eluting with 4% MeOH in DCM)

Sources & evidence

ORD record
ord-f63a1e954f6042c29519142ea1fecd78
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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