Sodium Carbonate → HCID 67250775, compound

HRID 391936Notes

Reaction equation

HRID 391936 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([CH3:34])[C:29]=3[CH3:35])=[CH:24][CH:23]=2)[CH2:16][C:15]2[CH:14]=[C:13]3[O:41][CH2:42][C@H:43]([C:45]4[CH:50]=[CH:49][C:48](OS(C(F)(F)F)(=O)=O)=[CH:47][CH:46]=4)[O:44][C:12]3=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:59][C:60]1[CH:61]=[C:62](B(O)O)[CH:63]=[CH:64][CH:65]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([CH3:34])[C:29]=3[CH3:35])=[CH:26][CH:27]=2)[CH2:16][C:15]2[CH:14]=[C:13]3[O:41][CH2:42][C@H:43]([C:45]4[CH:50]=[CH:49][C:48]([C:62]5[CH:63]=[CH:64][CH:65]=[C:60]([Cl:59])[CH:61]=5)=[CH:47][CH:46]=4)[O:44][C:12]3=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 86654943HCID 86654943, compound

Product 1

HCID 67250775HCID 67250775, compoundYield 54.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (3S,8S)-8-{(S)-2-[4-(2,3-Dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-3-(4-trifluoromethanesulfonyloxy-phenyl)-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (0.075 g) in toluene (4.0 mL) was added 3-chlorophenylboronic acid (0.0337 g), Pd(PPh3)4 (0.0052 g), and Na2CO3 (24 mg in 1.0 mL H2O). The mixture was heated at 90° C. for 3.0 hours. After completion of the reaction, the aqueous layer was drained. The organic layer was poured on to a silica gel column chromatography and eluted with 1% MeOH, 1:1 hexanes/EtOAc to provide (3S,8S)-3-(3′-Chloro-biphenyl-4-yl)-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (0.039 g) which was deprotected according to General Procedure C to provide (S)-2-{[(3S,8S)-3-(3′-Chloro-biphenyl-4-yl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester bis hydrochloride (0.025 g).

Workup

  1. customAfter completion of the reaction
  2. additionThe organic layer was poured on to a silica gel column chromatography
  3. washeluted with 1% MeOH, 1:1 hexanes/EtOAc

Sources & evidence

ORD record
ord-afc9a30b9b9c4f09bcf0bbcdea43138e
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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