4-Methylthiophene-2-carbonyl chloride → 1-Methyl-2-{2-[(4-methyl-thiophene-2-carbonyl)-amino]-pyrimidin-4-yl}-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 869330Notes

Reaction equation

HRID 869330 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH3:24])[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[N:18]=3)=[CH:16][C:10]=2[C:9]1=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26][C:27]1[CH:28]=[C:29]([C:32](Cl)=[O:33])[S:30][CH:31]=1>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH3:24])[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:32]([C:29]4[S:30][CH:31]=[C:27]([CH3:26])[CH:28]=4)=[O:33])[N:18]=3)=[CH:16][C:10]=2[C:9]1=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 27955254-Methylthiophene-2-carbonyl chlorideHCID 247765532-(2-Amino-pyrimidin-4-yl)-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 672847501-Methyl-2-{2-[(4-methyl-thiophene-2-carbonyl)-amino]-pyrimidin-4-yl}-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl esterYield 96.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

2-(2-Amino-pyrimidin-4-yl)-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (prepared as described in Example 9) (300 mg, 0.873 mmol) was suspended in dry pyridine under nitrogen atmosphere and sonicated for 2 minutes. 4-Methyl-thiophene-2-carbonyl chloride (0.142 mL, 1.135 mmol, 1.3 eq) and DMAP (10 mg, 0.087 mmol, 0.1 eq) were added and the mixture was stirred at room temperature for 3 hours. Pyridine was then evaporated and the residue was taken up with saturated aqueous NaHCO3 (10 mL) and extracted with ethyl acetate (3×10 mL). Combined organic layers were washed with brine (3×10 mL), dried over Na2SO4 and evaporated to dryness. The crude product was purified by chromatography on silica gel (gradient n-hexane/ethyl acetate 1:1 to pure ethyl acetate) to obtain 394 mg of 1-methyl-2-{2-[(4-methyl-thiophene-2-carbonyl)-amino]-pyrimidin-4-yl}-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (85%).

Workup

  1. customsonicated for 2 minutes
  2. customPyridine was then evaporated
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. washCombined organic layers were washed with brine (3×10 mL)
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness
  7. customThe crude product was purified by chromatography on silica gel (gradient n-hexane/ethyl acetate 1:1 to pure ethyl acetate)

Sources & evidence

ORD record
ord-6703c3d2ce27435288de567a68ed62a2
Source dataset
uspto-grants-2015_03
Patent number
US08969366B2

Reaction notes

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