Dicyclohexylcarbodiimide → tert-butyl-N-methyl-N-(1-{[6-(2-phenylethynyl)-4-(pyridin-4-yl)pyridin-2-yl]-carbamoyl}ethyl)carbamate

HRID 923669

Reaction equation

HRID 923669 reaction equation
[CH3:1][N:2]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:3]([CH3:7])[C:4]([OH:6])=O.C1(N=C=NC2CCCCC2)CCCCC1.[C:30]1([C:36]#[C:37][C:38]2[N:43]=[C:42]([NH2:44])[CH:41]=[C:40]([C:45]3[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=3)[CH:39]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN1C(=O)CCC1>[C:11]([O:10][C:8](=[O:9])[N:2]([CH3:1])[CH:3]([C:4](=[O:6])[NH:44][C:42]1[CH:41]=[C:40]([C:45]2[CH:46]=[CH:47][N:48]=[CH:49][CH:50]=2)[CH:39]=[C:38]([C:37]#[C:36][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:43]=1)[CH3:7])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 81531DiisopropylethylamineHCID 44368572-(((Tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 1179110016-(Phenylethynyl)-[4,4'-bipyridin]-2-amine

Product 1

HCID 117903139tert-butyl-N-methyl-N-(1-{[6-(2-phenylethynyl)-4-(pyridin-4-yl)pyridin-2-yl]-carbamoyl}ethyl)carbamate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid (1.44 g, 7.1 mmol) and N,N′-dicyclohexylcarbodiimide (0.73 g, 3.55 mmol) in DCM (4 ml) is stirred for 30 minutes at RT. This mixture is added in 4 portions over 48 h via syringe filter to a mixture of 6-(2-phenylethynyl)-4-(pyridin-4-yl)pyridin-2-amine G1 (0.24 g, 0.89 mmol), DIPEA (166 μl, 0.98 mmol) and NMP (2 ml) at 50° C. After stirring for another 16 h at 50° C. the mixture is filtered and the product purified by RP HPLC. Yield: 56 mg (14%). HPLC-MS: M+H=457; tR=.2.08 min (METHOD—2).

Workup

  1. additionThis mixture is added in 4 portions over 48 h via syringe
  2. stirringAfter stirring for another 16 h at 50° C. the mixture
  3. filtrationis filtered
  4. customthe product purified by RP HPLC
  5. custom2.08 min (METHOD—2)

Sources & evidence

ORD record
ord-24de4df4926842b28a6435c149caebc5
Source dataset
uspto-grants-2016_03
Patent number
US09278978B2

Linked notes

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