Methylamine → 2-(ethylamino)-N-[5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-yl]butanamide

HRID 535423Notes

Reaction equation

HRID 535423 reaction equation
[N:1]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]([NH2:25])=[N:11][C:12]=2[C:13]#[C:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[N:21]=[CH:20][CH:19]=[CH:18]3)[CH:4]=[N:3][CH:2]=1.[CH3:26][CH2:27][N:28](C(C)C)C(C)C.Br[CH:36]([CH2:40][CH3:41])[C:37](Br)=[O:38].CN>C(Cl)Cl.C1COCC1.CN1C(=O)CCC1>[CH2:27]([NH:28][CH:36]([CH2:40][CH3:41])[C:37]([NH:25][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[CH:6]=[N:1][CH:2]=[N:3][CH:4]=2)=[C:12]([C:13]#[C:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[N:21]=[CH:20][CH:19]=[CH:18]3)[N:11]=1)=[O:38])[CH3:26]

Participants

8

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 1172932-Bromobutanoyl bromideHCID 866944135-Pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-amine

Product 1

HCID 866944122-(ethylamino)-N-[5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-yl]butanamide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-amine G2b (600 mg, 1.86 mmol) is mixed with NMP (10 ml) and DIPEA (1.42 ml, 8.35 mmol). 2-Bromobutanoyl bromide (985 μl, 8.17 mmol) is added dropwise. The mixture stirred for 1 h at RT. The mixture is diluted with DCM and extracted with a saturated aqueous solution of NaHCO3. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The crude intermediate is mixed with a THF solution of methylamine (2 mol/l, 5 ml, 10 mmol) and stirred at RT for 16 h. The mixture is diluted with DCM and extracted with a saturated aqueous solution of NaHCO3. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 250 mg (32%). HPLC-MS: M+H=423; tR=1.25 min (*Method—1).

Workup

  1. extractionextracted with a saturated aqueous solution of NaHCO3
  2. dry with materialThe combined organic layers are dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. stirringstirred at RT for 16 h
  5. extractionextracted with a saturated aqueous solution of NaHCO3
  6. dry with materialThe combined organic layers are dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe product is purified by RP HPLC

Sources & evidence

ORD record
ord-c2813ae979d3436c916f4e26cc601651
Source dataset
uspto-grants-2014_10
Patent number
US08859541B2

Reaction notes

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