Water → HCID 178508594, compound

HRID 422674Notes

Reaction equation

HRID 422674 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]([CH2:16][OH:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:18]1([C:24]2[CH:33]=[CH:32][C:31]3[C:26](=[CH:27][C:28](B4OC(C)(C)C(C)(C)O4)=[CH:29][CH:30]=3)[N:25]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+].O>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>[NH2:1][C:2]1[C:3]2[C:10]([C:28]3[CH:27]=[C:26]4[C:31]([CH:32]=[CH:33][C:24]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)=[N:25]4)=[CH:30][CH:29]=3)=[CH:9][N:8]([C@H:12]3[CH2:15][C@H:14]([CH2:16][OH:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 536290112-Phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolineHCID 178508629HCID 178508629, compound

Product 1

HCID 178508594HCID 178508594, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Following the general procedure for the Suzuki coupling, trans-[3-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutyl]-methanol (139.2 mg, 0.4045 mmol) was reacted with 2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline (141 mg, 0.426 mmol), Na2CO3 (107 mg, 1.01 mmol) and Pd(PPh3)4 (30 mg, 0.026 mmol) in DMF (10 mL)/water (2 mL). The crude material was purified by column chromatography on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with CH2Cl2 (1-7)→2% MeOH in CH2Cl2 (8-22)→5% MeOH in CH2Cl2 (23-41)→7% MeOH in CH2Cl2 (42-51)], yielding the title compound. 1H NMR (CDCl3, 400 MHz) δ 2.42-2.60 (m, 3H), 2.60-2.73 (m, 3H), 3.88 (d, J=6.4 Hz, 2H), 5.19 (brs, 2H), 5.44-5.53 (mc, 1H), 7.39 (s, 1H), 7.46-7.52 (m, 1H), 7.52-7.58 (m, 2H), 7.71 (dd, J=1.7, 8.3 Hz, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.94 (d, J=7.7 Hz, 1H), 8.17-8.22 (m, 2H), 8.27 (d, J=8.5 Hz, 1H), 8.29-8.32 (m, 1H), 8.36 (s, 1H). 13C NMR (CDCl3, 100.6 MHz, DEPT135) δ 30.62 (+), 32.16 (2C, −), 46.70 (+), 65.12 (−), 101.04 (Cquart), 116.13 (Cquart), 118.88 (+), 120.64 (+), 125.82 (Cquart), 127.27 (+), 127.45 (2C, +), 128.17 (+), 128.21 (+), 128.71 (2C, +), 129.40 (+), 136.23 (Cquart), 136.49 (+), 139.23 (Cquart), 148.28 (Cquart), 150.47 (Cquart), 151.57 (+), 157.09 (Cquart), 157.97 (Cquart). MS (ES+): m/z 422.1 (51) [MH+], 338.2 (39) [MH+−cyclobutene-CH2OH]. HPLC: tR=2.4 min (OpenLynx, polar—5 min).

Workup

  1. customThe crude material was purified by column chromatography on silica gel [Jones Flashmaster, 10 g/70 mL cartridge
  2. washeluting with CH2Cl2 (1-7)→2% MeOH in CH2Cl2 (8-22)→5% MeOH in CH2Cl2 (23-41)→7% MeOH in CH2Cl2 (42-51)],

Sources & evidence

ORD record
ord-1180cace90894cc7b74e6c63519a29da
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

Loading…