Dimethylformamide → HCID 178508593, compound

HRID 386259Notes

Reaction equation

HRID 386259 reaction equation
[NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@H:12]3[CH2:15][C@H:14]([C:16]([NH2:18])=[O:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:19]1([C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][C:29](B4OC(C)(C)C(C)(C)O4)=[CH:30][CH:31]=3)[N:26]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:1][C:2]1[C:3]2[C:10]([C:29]3[CH:28]=[C:27]4[C:32]([CH:33]=[CH:34][C:25]([C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)=[N:26]4)=[CH:31][CH:30]=3)=[CH:9][N:8]([C@H:12]3[CH2:15][C@H:14]([C:16]([NH2:18])=[O:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 536290112-Phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolineHCID 178508627HCID 178508627, compound

Product 1

HCID 178508593HCID 178508593, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of trans-3-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutanecarboxylic acid amide (119 mg, 0.333 mmol), 2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline (133 mg, 0.402 mmol), Na2CO3 (88.3 mg, 0.833 mmol), Pd(PPh3)4 (23.1 mg, 0.0200 mmol), DMF (5 mL), and water (1 mL) was purged with nitrogen for 30 min and heated to 80° C. for 22 h. To the cooled reaction solution was added water (10 mL), the mixture was extracted with EtOAc (3×15 mL), the combined organic layers were washed with water (2×10 mL) and brine, dried over MgSO4, filtered, and concentrated. The residue was triturated with MeOH to give the title compound as light yellow solid. Chromatography of the mother liquor on silica gel (8 g, eluting with 2%→4%→6%→8%→10% MeOH in CH2Cl2) gave an additional batch. Both batches contained a small amount of the corresponding cis isomer (see below for its independent synthesis). 1H NMR (CDCl3, 400 MHz): δ=2.70-2.78 (m, 2 H), 2.97-3.08 (m, 2 H), 3.21-3.26 (m, 1 H), 5.66-5.72 (quintet, 1 H, J=8.4 Hz), 6.54 (brs, 2 H), 7.08 (s, 1 H), 7.59 (s, 1 H), 7.68-7.78 (m, 3 H), 7.94-7.98 (m, 1 H), 8.12 (s, 1 H), 8.26-8.28 (d, 1 H, J=8.4 Hz), 8.32-8.37 (m, 3 H), 8.48-8.53 (m, 2 H), 8.66-8.68 (d, 1 H, J=8.8 Hz). MS (ES+): 435.2 [MH+]. HPLC: tR=2.3 min (polar—5 min).

Workup

  1. customwas purged with nitrogen for 30 min
  2. customTo the cooled reaction solution
  3. extractionthe mixture was extracted with EtOAc (3×15 mL)
  4. washthe combined organic layers were washed with water (2×10 mL) and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was triturated with MeOH

Sources & evidence

ORD record
ord-2561eaefd602414199ba775c23fc9d8f
Source dataset
uspto-grants-2013_02
Patent number
US08367826B2

Reaction notes

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