Triethylamine → HCID 178523053, compound

HRID 1831977Notes

Reaction equation

HRID 1831977 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[C:8]([F:10])[C:7]([N:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[C:13]([Cl:27])[C:12]2=[O:28])=[C:6]([F:29])[CH:5]=1.C(N(CC)CC)C.[NH:37]1[CH:41]=[C:40]([C:42](O)=[O:43])[N:39]=[CH:38]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[Cl:27][C:13]1[C:12](=[O:28])[N:11]([C:7]2[C:6]([F:29])=[CH:5][C:4]([CH2:3][NH:2][C:42]([C:40]3[N:39]=[CH:38][NH:37][CH:41]=3)=[O:43])=[CH:9][C:8]=2[F:10])[CH:16]=[CH:15][C:14]=1[O:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=1[F:26]

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22050916HCID 22050916, compound2×HCID 178524800HCID 178524800, compound

Product 1

HCID 178523053HCID 178523053, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-[4-(aminomethyl)-2,6-difluorophenyl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]pyridin-2(1H)-one hydrochloride (150 mg, 0.334 mmol) is dissolved in a solution of 4 ml tetrahydrofuran and triethylamine (35 mg, 0.35 mmol). 4-imidazolecarboxylic acid (62 mg, 0.56 mmol), 1-hydroxybenzotriazole hydrate (90 mg, 0.67 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (128 mg, 0.668 mmol), and triethylamine (100 mg, 0.989 mmol) were combined in 5 ml tetrahydrofuran and stirred under nitrogen. The solution containing 1-[4-(aminomethyl)-2,6-difluorophenyl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]pyridin-2(1H)-one hydrochloride was added in one portion, rinsing with 2 ml tetrahydrofuran. Stirring was continued at room temperature overnight, then the reaction was poured into 90 ml of icewater, and the product collected by filtration and dired in vacuo (254 mg, 94%). 1H-NMR (400 MHz, DMSO-d6) δ 12.55 (br s, 1H), 8.73 (t, J=6.57 Hz, 1H), 7.90 (d, J=7.87 Hz, 1H), 7.75 (s, 1H), 7.67 (m, 2H), 7.35, (dt, J=10.04, 2.54 Hz, 1H), 7.21 (m, 3H), 6.78 (d, J=8.04 Hz, 1H), 5.39 (s, 2H), 4.47 (m, 2H), 1 9F-NMR (400 MHz, DMSO-d6) δ−109.26 (quintet, J=7.87 Hz, 1F), −113.52 (quartet, J=9.30 Hz, 1F), −120.59 (d, J=9.21 Hz, 2F). LC/MS tr=4.48 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50° C.) ES-MS m/z 507 (M+H). ES-HRMS m/z 507.0818 (M+H calcd for C23H16ClF4N4O3 requires 507.0842).

Workup

  1. additionwas added in one portion
  2. washrinsing with 2 ml tetrahydrofuran
  3. stirringStirring
  4. additionthe reaction was poured into 90 ml of icewater
  5. filtrationthe product collected by filtration and dired in vacuo (254 mg, 94%)
  6. customLC/MS tr=4.48 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50° C.) ES-MS m/z 507 (M+H)

Sources & evidence

ORD record
ord-958a077f41e54d7bb9ca74521a8b6cd7
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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