Nitrogen → HCID 178472381, compound

HRID 1028794Notes

Reaction equation

HRID 1028794 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@@H:9]([N:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([NH2:21])[C:15]=3[C:14](I)=[CH:13]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[C:23]1([C:29]2[CH:38]=[CH:37][C:36]3[C:31](=[CH:32][C:33](B4OC(C)(C)C(C)(C)O4)=[CH:34][CH:35]=3)[N:30]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+].N#N>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>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@@H:9]([N:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([NH2:21])[C:15]=3[C:14]([C:33]3[CH:32]=[C:31]4[C:36]([CH:37]=[CH:38][C:29]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)=[N:30]4)=[CH:35][CH:34]=3)=[CH:13]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 536290112-Phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolineHCID 178472387HCID 178472387, compound

Product 1

HCID 178472381HCID 178472381, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of cis-4-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclohexanecarboxylic acid ethyl ester (16.2 mg 0.0391 mmol), 2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline (15.6 mg, 1.2 eq.), Pd(PPh3)4 (2.7 mg, 0.06 eq.) and Na2CO3 (10.4 mg, 2.5 eq.) in DMF (2.5 mL)/H2O (0.5 mL) was flushed with N2 for 30 min at rt and heated at 80° C. for 16 h under nitrogen. After that time, the reaction mixture was treated with H2O and extracted with EtOAc (3×10 mL). The combined extracts were washed with H2O (2×5 mL) and brine (5 mL), and dried over MgSO4. The drying agent was filtered off, the filtrate was concentrated in vacuo, and the crude yellow oil was purified by HPLC to obtain the title compound as yellow oil. 1H NMR (CDCl3, 400 MHz): δ=1.29-1.36 (t, 3H, J=7.2 Hz), 1.74-2.09 (m, 6H), 2.34-2.41 (m, 2H), 2.75 (m, 1H), 4.19-4.25 (q, 2H, J=7.2 Hz), 4.77-4.85 (m, 1H), 5.22 (brs, 2H), 7.22 (s, 1H), 7.46-7.57 (m, 3H), 7.68-7.70 (dd, 1H, J=1.6 & 8.0 Hz), 7.89-7.93 (m, 2H), 8.18-8.20 (dd, 2H, J=0.8 & 8.0 Hz), 8.25-8.27 (m, 2H), 8.37 (s, 1H). MS (ES+): 492.1 [MH+]. HPLC: tR=3.1 min (polar—5 min).

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. washThe combined extracts were washed with H2O (2×5 mL) and brine (5 mL)
  3. dry with materialdried over MgSO4
  4. filtrationThe drying agent was filtered off
  5. concentrationthe filtrate was concentrated in vacuo
  6. customthe crude yellow oil was purified by HPLC

Sources & evidence

ORD record
ord-44a6aef2afb04e28b4b741324f2f84d6
Source dataset
uspto-grants-2014_05
Patent number
US08735405B2

Reaction notes

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