1,2-Dichloroethane → HCID 59375073, compound

HRID 661972Notes

Reaction equation

HRID 661972 reaction equation
[NH2:1][C:2]1[C:3]([CH3:35])=[C:4]([C:8]2[CH:20]=[CH:19][C:18]([C:21](=[O:23])[NH2:22])=[C:17]3[C:9]=2[C:10]2[CH:11]=[CH:12][C:13]([NH:24][C:25](=[O:34])[O:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:14][C:15]=2[NH:16]3)[CH:5]=[CH:6][CH:7]=1.[F:36][C:37]1[CH:38]=[CH:39][C:40]([C:43](O)=[O:44])=[N:41][CH:42]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1>[C:21]([C:18]1[CH:19]=[CH:20][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:43](=[O:44])[C:40]3[CH:39]=[CH:38][C:37]([F:36])=[CH:42][N:41]=3)[C:3]=2[CH3:35])=[C:9]2[C:17]=1[NH:16][C:15]1[CH:14]=[C:13]([NH:24][C:25](=[O:34])[O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:12]=[CH:11][C:10]2=1)(=[O:23])[NH2:22]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27628765-fluoropyridine-2-carboxylic AcidHCID 59375075HCID 59375075, compound

Product 1

HCID 59375073HCID 59375073, compoundYield 37.2%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

A mixture of benzyl 5-(3-amino-2-methylphenyl)-8-carbamoyl-9H-carbazol-2-ylcarbamate (Example 51-2, 100 mg, 0.215 mmol), 5-fluoropicolinic acid (45.6 mg, 0.323 mmol), HOAT (44.0 mg, 0.323 mmol), and EDC (83 mg, 0.431 mmol) in DCM-THF (80:20, 12 mL) was treated with DIEA (0.150 mL, 0.861 mmol) and the solution was stirred at rt overnight. The mixture was concentrated and purified by preparative HPLC to provide benzyl 8-carbamoyl-5-(3-(5-fluoropicolinamido)-2-methylphenyl)-9H-carbazol-2-ylcarbamate as a white solid (47 mg, 36%). 1H NMR (400 MHz, DMSO-d6) δ 11.48 (1H, s), 10.41 (1H, s), 9.83 (1H, s), 8.74 (1H, d, J=3.0 Hz), 8.27 (1H, dd, J=8.8, 4.8 Hz), 8.09-8.21 (1H, m), 7.96-8.03 (2H, m), 7.94 (1H, d, J=7.8 Hz), 7.85 (1H, d, J=7.5 Hz), 7.29-7.51 (7H, m), 7.15-7.21 (1H, m), 6.91-6.98 (2H, m), 6.79 (1H, d, J=8.8 Hz), 5.16 (2H, s), 1.96 (3H, s). Mass spectrum m/z 588.1 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-f240083559154fedaecc7ee439ebb124
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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