Bromocyclopropane → HCID 178426870, compound

HRID 561956Notes

Reaction equation

HRID 561956 reaction equation
[CH3:1][C:2]1[CH:39]=[C:38]([CH3:40])[CH:37]=[CH:36][C:3]=1[O:4][CH2:5][C@H:6]([OH:35])[CH2:7][NH:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[C:10]=1[C:16]1[NH:27][C:26]2[C:18](=[CH:19][C:20]3[CH2:21][N:22]([CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)[C:23](=[O:28])[C:24]=3[CH:25]=2)[N:17]=1.Br[CH:42]1[CH2:44][CH2:43]1.CCN(C(C)C)C(C)C>CC#N>[CH:42]1([N:32]2[CH2:31][CH2:30][CH:29]([N:22]3[CH2:21][C:20]4[CH:19]=[C:18]5[C:26]([NH:27][C:16]([C:10]6[C:11](=[O:15])[NH:12][CH:13]=[CH:14][C:9]=6[NH:8][CH2:7][CH:6]([OH:35])[CH2:5][O:4][C:3]6[CH:36]=[CH:37][C:38]([CH3:40])=[CH:39][C:2]=6[CH3:1])=[N:17]5)=[CH:25][C:24]=4[C:23]3=[O:28])[CH2:34][CH2:33]2)[CH2:44][CH2:43]1

Participants

5

Reactant 3

HCID 78037BromocyclopropaneHCID 81531DiisopropylethylamineHCID 1784268602-(4-[(R)-3-(2,4-dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl)-6-piperidin-4-yl-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-one

Product 1

HCID 178426870HCID 178426870, compoundYield 5.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-{4-[(R)-3-(2,4-dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-piperidin-4-yl-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-one (54.3 mg, 0.1 mmol) and bromocyclopropane (121 mg, 1.0 mmol) in CH3CN (8 mL) was added DIEA (129.3 mg, 1.0 mmol) and the resulting reaction mixture was stirred at the room temperature for 112 h and then evaporated. Chromatography of the residue with CH2Cl2/MeOH/28% aqueous NH4OH (490:10:1) afforded the title compound (3.27 mg, 5.6%). 1H NMR (DMSO-d6) δ 1.70 (m, 2H), 1.80 (m, 2H), 2.04 (m, 2H), 2.19 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.90-3.00 (4H), 3.45 (m, 1H), 3.70 (m, 1H), 3.95-4.06 (3H), 4.11 (m, 1H), 4.42 (s, 1H), 4.47 (s, 1H), 5.10-5.22 (2H), 5.47 (d, J=3 Hz, 0.5H, NH), 5.52 (d, J=3 Hz, 0.5H, NH), 5.81 (m, 1H), 6.22 (m, 1H), 6.81 (m, 1H), 6.89-6.99 (2H), 7.32-7.38 (1.5H), 7.68 (s, 0.5H), 7.80 (s, 0.5H), 7.94 (s, 0.5H), 11.15 (d, J=6 Hz, 1H, NH), 11.21 (br d, J=6 Hz, 1H, NH); ESI-MS m/z 583.7 (MH+).

Workup

  1. customthe resulting reaction mixture
  2. customevaporated

Sources & evidence

ORD record
ord-917e8035d77c442aab1be77aca7fabaf
Source dataset
uspto-grants-2011_11
Patent number
US08063225B2

Reaction notes

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