Dimethylformamide → HCID 178508590, compound

HRID 244181Notes

Reaction equation

HRID 244181 reaction equation
CN(C=O)C.[N:6]1([CH2:10][C@@H:11]2[CH2:14][C@H:13]([N:15]3[C:19]4[N:20]=[CH:21][N:22]=[C:23]([NH2:24])[C:18]=4[C:17](I)=[CH:16]3)[CH2:12]2)[CH2:9][CH2:8][CH2:7]1.[C:26]1([C:32]2[CH:41]=[CH:40][C:39]3[C:34](=[CH:35][C:36](B4OC(C)(C)C(C)(C)O4)=[CH:37][CH:38]=3)[N:33]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([O-])([O-])=O.[Na+].[Na+]>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>[N:6]1([CH2:10][C@@H:11]2[CH2:14][C@H:13]([N:15]3[C:19]4[N:20]=[CH:21][N:22]=[C:23]([NH2:24])[C:18]=4[C:17]([C:36]4[CH:35]=[C:34]5[C:39]([CH:40]=[CH:41][C:32]([C:26]6[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=6)=[N:33]5)=[CH:38][CH:37]=4)=[CH:16]3)[CH2:12]2)[CH2:9][CH2:8][CH2:7]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium Carbonate2×HCID 536290112-Phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolineHCID 178508625HCID 178508625, compound

Product 1

HCID 178508590HCID 178508590, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To the DMF solution from the preparation of cis-7-(3-azetidin-1-ylmethylcyclobutyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine were added 2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline (40 mg, 0.12 mmol), Na2CO3 (27 mg, 0.25 mmol), Pd(PPh3)4 (7 mg, 0.006 mmol), and water (0.6 mL). The solution was purged with nitrogen for 10 min and heated to 80° C. for 16 h. To the cooled reaction solution was added sat. Na2CO3 solution (10 mL), the mixture was extracted with EtOAc (3×20 mL), the combined organic layers were washed with water (3×15 mL) and brine, dried over MgSO4, filtered, and concentrated to give a brown oil. Purification by HPLC gave the title compound as brown oil. 1H NMR (CDCl3, 400 MHz): δ=2.06-2.26 (m, 5H), 2.56-2.57 (d, 2H, J=6.2), 2.71-2.77 (m, 2H), 3.21-3.24 (m, 4H), 5.17 (brs, 2H), 5.19-5.26 (m, 1H), 7.31 (s, 1H), 7.46-7.56 (m, 3H), 7.69-7.71 (dd, 1H, J=1.6 & 8.4 Hz), 7.90-7.94 (m, 2H), 8.18-8.20 (m, 2H), 8.26-8.29 (m, 2H), 8.35 (s, 1H). MS (ES+): 461.2 [MH+]. HPLC: tR=2.0 min (polar—5 min).

Workup

  1. customThe solution was purged with nitrogen for 10 min
  2. customTo the cooled reaction solution
  3. extractionthe mixture was extracted with EtOAc (3×20 mL)
  4. washthe combined organic layers were washed with water (3×15 mL) and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a brown oil
  9. customPurification by HPLC

Sources & evidence

ORD record
ord-fe6932b3bc7847b5a5e6ce99f5f8aea0
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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