4-Methylmorpholine → 6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid [4-(2-isopropoxy-ethylcarbamoyl)-pyridin-3-yl]-amide

HRID 2368322Notes

Reaction equation

HRID 2368322 reaction equation
[CH:1]([O:4][CH2:5][CH2:6][NH2:7])([CH3:3])[CH3:2].[CH:8]1([C:11]2[N:16]=[C:15]([C:17]([NH:19][C:20]3[CH:28]=[N:27][CH:26]=[CH:25][C:21]=3[C:22](O)=[O:23])=[O:18])[C:14]([NH:29][C:30]3[CH:31]=[N:32][CH:33]=[N:34][CH:35]=3)=[N:13][CH:12]=2)[CH2:10][CH2:9]1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[CH:1]([O:4][CH2:5][CH2:6][NH:7][C:22]([C:21]1[CH:25]=[CH:26][N:27]=[CH:28][C:20]=1[NH:19][C:17]([C:15]1[C:14]([NH:29][C:30]2[CH:35]=[N:34][CH:33]=[N:32][CH:31]=2)=[N:13][CH:12]=[C:11]([CH:8]2[CH2:10][CH2:9]2)[N:16]=1)=[O:18])=[O:23])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 5338662-(Propan-2-yloxy)ethan-1-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 700989283-{[6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carbonyl]-amino}-isonicotinic acid

Product 1

HCID 585481776-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid [4-(2-isopropoxy-ethylcarbamoyl)-pyridin-3-yl]-amideYield 80.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 2-aminoethyl isopropyl ether (25 mg, 242 μmol) and 3-{[6-cyclopropyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carbonyl]-amino}-isonicotinic acid (101 mg, 267 μmol) at rt in THF (5 ml) under an argon atmosphere were added 4-methylmorpholine (123 mg, 134 μl, 1.21 mmol) and HATU (184 mg, 485 μmol). The mixture was heated to reflux and stirring was continued for 1 day. The reaction mixture was concentrated. The crude product was purified by silica gel chromatography using an EtOAc/MeOH gradient as eluent. After trituration with MeOH, the title compound (90 mg, 80%) was obtained as yellow solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. concentrationThe reaction mixture was concentrated
  4. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e19b341a1c3b43cdb362ff9e79dec06a
Source dataset
uspto-grants-2014_04
Patent number
US08703768B2

Reaction notes

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