Diisopropylethylamine → 9H-fluoren-9-ylmethyl [2-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)-2-oxoethyl]carbamate

HRID 1504872Notes

Reaction equation

HRID 1504872 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[N:12]=2)[C:5]([C:8]#[N:9])=[N:6][CH:7]=1.Cl[C:20](=[O:40])[CH2:21][NH:22][C:23](=[O:39])[O:24][CH2:25][CH:26]1[C:38]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[C:32]2[C:27]1=[CH:28][CH:29]=[CH:30][CH:31]=2.C(N(C(C)C)CC)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CN(C=O)C.C(OCC)(=O)C>[C:8]([C:5]1[N:6]=[CH:7][C:2]([NH:1][C:20](=[O:40])[CH2:21][NH:22][C:23](=[O:39])[O:24][CH2:25][CH:26]2[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:32]=3[C:33]3[C:38]2=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:3][C:4]=1[NH:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[N:12]=1)#[N:9]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 11758879Fmoc-Gly-ClHCID 867316535-Amino-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrile

Product 1

HCID 867317419H-fluoren-9-ylmethyl [2-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)-2-oxoethyl]carbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-amino-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrile (PrepEx 1.8) (100 mg, 0.418 mmol), 9H-fluoren-9-ylmethyl (2-chloro-2-oxoethyl)carbamate (264 mg, 0.835 mmol), and diisopropylethylamine (0.15 mL, 0.84 mmol) in DMF (3.2 mL) at 0° C. was added 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate, 0.29 mL, 0.50 mmol). The reaction mixture was stirred for 2 hours while warming to room temperature. The reaction mixture was diluted with ethyl acetate and washed with sodium hydroxide (1.0 M in water). The organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Dichloromethane (3 mL) was slowly added, and the precipitated solids were filtered and collected to afford 9H-fluoren-9-ylmethyl [2-({6-cyano-5-[(4,6-dimethylpyridin-2-yl)amino]pyridin-3-yl}amino)-2-oxoethyl]carbamate. MS ESI calc'd for C30H27N6O3 [M+H]+ 519. found 519. 1H NMR (500 MHz, DMSO-d6) δ 10.54 (s, 1H), 9.09 (s, 1H), 8.78 (d, J=2.0 Hz, 1H), 8.39 (d, J=2.1 Hz, 1H), 7.88 (d, J=7.5 Hz, 2), 7.75-7.65 (m, 3H), 7.40 (t, J=7.4 Hz, 2H), 7.31 (t, J=7.4 Hz, 2H), 6.65 (s, 1H), 6.61 (s, 1H), 4.29 (d, J=7.0 Hz, 2), 4.24-4.20 (m, 1H), 3.84 (d, J=6.1 Hz, 2H), 2.28 (s, 3H), 2.20 (s, 3H).

Workup

  1. washwashed with sodium hydroxide (1.0 M in water)
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. additionDichloromethane (3 mL) was slowly added
  6. filtrationthe precipitated solids were filtered
  7. customcollected

Sources & evidence

ORD record
ord-cac2e8c48d514bac954b820e3ff40d37
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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