1,2-Dichloroethane → HCID 59375047, compound

HRID 1811174Notes

Reaction equation

HRID 1811174 reaction equation
[NH2:1][C:2]1[C:3]([CH3:28])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([CH:21]([OH:24])[CH2:22][OH:23])=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:25]([NH2:27])=[O:26])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[F:29][C:30]1[CH:31]=[CH:32][C:33]([C:36](O)=[O:37])=[N:34][CH:35]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>C(#N)C.C1COCC1>[OH:24][CH:21]([C:16]1[CH:15]=[C:14]2[C:19]([C:20]3[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:36](=[O:37])[C:33]5[CH:32]=[CH:31][C:30]([F:29])=[CH:35][N:34]=5)[C:3]=4[CH3:28])=[CH:9][CH:10]=[C:11]([C:25]([NH2:27])=[O:26])[C:12]=3[NH:13]2)=[CH:18][CH:17]=1)[CH2:22][OH:23]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27628765-fluoropyridine-2-carboxylic AcidHCID 66606251HCID 66606251, compound

Product 1

HCID 59375047HCID 59375047, compoundYield 53.5%

Reagents, catalysts & solvents 1

HCID 22177404Acetonitrile tetrahydrofuranSolvent

Procedure

A solution of 4-(3-amino-2-methylphenyl)-7-(1,2-dihydroxyethyl)-9H-carbazole-1-carboxamide (Example 70-4, 28 mg, 0.075 mmol), 5-fluoropicolinic acid (15.8 mg, 0.112 mmol), HOAT (18.3 mg, 0.134 mmol), and EDC (28.6 mg, 0.149 mmol) in acetonitrile-THF (2:1, 3 mL) was treated with DIEA (0.039 mL, 0.224 mmol) and stirred at rt overnight. The mixture was concentrated and purified by preparative HPLC. The residue from concentration of the appropriate effluent fractions was partitioned between NaHCO3 (aq) and EtOAc, and the organic phase was washed with brine, dried and concentrated to provide 7-(1,2-dihydroxyethyl)-4-(3-(5-fluoropicolinamido)-2-methylphenyl)-9H-carbazole-1-carboxamide as an off-white solid (20 mg, 53%). 1H NMR (400 MHz, DMSO-d6) δ 11.47 (1H, s), 10.38 (1H, s), 8.74 (1H, d, J=2.6 Hz), 8.28 (1H, dd, J=8.8, 4.8 Hz), 8.10-8.23 (1H, m), 7.95-8.04 (2H, m), 7.87-7.93 (1H, m), 7.72 (1H, s), 7.46-7.52 (1H, m), 7.43 (1H, t, J=7.6 Hz), 7.18 (1H, d, J=6.6 Hz), 6.97 (1H, d, J=7.7 Hz), 6.82-6.92 (2H, m), 5.22 (1H, t, J=3.5 Hz), 4.66-4.72 (1H, m), 4.56-4.64 (1H, m), 3.44 (2H, t, J=6.1 Hz), 1.97 (3H, s). Mass spectrum m/z 521.3 (M+Na)+.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC
  3. customThe residue from concentration of the appropriate effluent fractions was partitioned between NaHCO3 (aq) and EtOAc
  4. washthe organic phase was washed with brine
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-06bc572ddcc549a9b435ca439f59f018
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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