Toluene → 4-{4-[3-(Cyclopropyl-benzoylamino)-5-fluoro-2-methyl-phenyl]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 589503Notes

Reaction equation

HRID 589503 reaction equation
C1([C:4]2[CH:12]=[CH:11][C:7]([C:8](O)=[O:9])=[CH:6][CH:5]=2)CC1.S(Cl)(Cl)=O.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH:28]=[C:27]([C:30]2[NH:47][C:33]3[N:34]=[CH:35][N:36]=[C:37]([C:38]4[CH:43]=[C:42]([F:44])[CH:41]=[C:40]([NH2:45])[C:39]=4[CH3:46])[C:32]=3[CH:31]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].[C:48]1([CH3:54])C=CC=C[CH:49]=1>N1C=CC=CC=1>[C:17]([O:21][C:22]([N:24]1[CH2:25][CH:26]=[C:27]([C:30]2[NH:47][C:33]3[N:34]=[CH:35][N:36]=[C:37]([C:38]4[CH:43]=[C:42]([F:44])[CH:41]=[C:40]([N:45]([CH:54]5[CH2:48][CH2:49]5)[C:8](=[O:9])[C:7]5[CH:11]=[CH:12][CH:4]=[CH:5][CH:6]=5)[C:39]=4[CH3:46])[C:32]=3[CH:31]=2)[CH2:28][CH2:29]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 4

HCID 1140TolueneHCID 24386Thionyl ChlorideHCID 2820644-Cyclopropylbenzoic acidHCID 867309964-[4-(3-Amino-5-fluoro-2-methyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 867309954-{4-[3-(Cyclopropyl-benzoylamino)-5-fluoro-2-methyl-phenyl]-7H-pyrrolo[2,3-d]pyrimidin-6-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-cyclopropyl benzoic acid (0.58 g, 3.57 mmol) in toluene (2 ml), thionyl chloride (1.29 ml, 17.87 mmol) was added. The mixture was stirred at 80° C. for 2 hours and afterwards evaporated under reduced pressure. The residue was dissolved together with Intermediate 20 (1.0 g, 2.36 mmol) in pyridine (5 ml) and the mixture was stirred at room temperature for 2 hours. Pyridine was evaporated under reduced pressure and the residue was dissolved in DCM and washed with saturated sodium hydrogen carbonate solution and brine (2×). The residue was purified by flash chromatography on silica (cyclohexane to EtOAc) to afford the compound Intermediate 21 as a beige solid.

Workup

  1. customafterwards evaporated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 2 hours
  3. customPyridine was evaporated under reduced pressure
  4. dissolutionthe residue was dissolved in DCM
  5. washwashed with saturated sodium hydrogen carbonate solution and brine (2×)
  6. customThe residue was purified by flash chromatography on silica (cyclohexane to EtOAc)

Sources & evidence

ORD record
ord-199a934346b34359bfe47368f9b1dc0f
Source dataset
uspto-grants-2016_01
Patent number
US09233111B2

Reaction notes

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