Sodium Bicarbonate → (S)-tert-butyl (1-((3-(6-((3-fluorophenyl)amino)-4-(propylamino)nicotinamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284812Notes

Reaction equation

HRID 2284812 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:17]=[C:16]([NH:18][CH2:19][CH2:20][CH3:21])[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:22][C:23]1[CH:24]=[C:25]([NH:29][C:30](=[O:42])[C@@H:31]([N:33]([CH3:41])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH3:32])[CH:26]=[CH:27][CH:28]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O.C(N(CC)C(C)C)(C)C>[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:17]=[C:16]([NH:18][CH2:19][CH2:20][CH3:21])[C:12]([C:13]([NH:22][C:23]3[CH:24]=[C:25]([NH:29][C:30](=[O:42])[C@@H:31]([N:33]([CH3:41])[C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:39])[CH3:38])[CH3:32])[CH:26]=[CH:27][CH:28]=3)=[O:15])=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 90051717(S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamateHCID 900521806-((3-Fluorophenyl)amino)-4-(propylamino)nicotinic acid

Product 1

HCID 90052372(S)-tert-butyl (1-((3-(6-((3-fluorophenyl)amino)-4-(propylamino)nicotinamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamateYield 72.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 6-((3-fluorophenyl)amino)-4-(propylamino)nicotinic acid (S16, 87 mg), (S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (B9, 115 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (115 mg) and 1-hydroxybenzotriazole monohydrate (81 mg) in N,N-dimethylformamide (2 mL), N,N-diisopropylethylamine (157 μL) was added at room temperature, and the mixture was stirred at 40° C. for 15 hours. The reaction mixture was cooled to room temperature, and then saturated aqueous sodium hydrogencarbonate was added to the reaction mixture. The solid matter was taken by filtration, washed with water, and then purified by silica gel column chromatography (eluent, 75 to 35% hexane in ethyl acetate) to obtain (S)-tert-butyl (1-((3-(6-((3-fluorophenyl)amino)-4-(propylamino)nicotinamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (S17, 123 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe solid matter was taken by filtration
  3. washwashed with water
  4. custompurified by silica gel column chromatography (eluent, 75 to 35% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-abfd272ff19245419ccf6e286a1e439c
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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