Bromocyclopropane → HCID 178426870, compound

HRID 2361196Notes

Reaction equation

HRID 2361196 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-60847ff72e934ef393720e2d2d59a4ce
Source dataset
uspto-grants-2014_04
Patent number
US08686005B2

Reaction notes

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