1,2-Dichloroethane → HCID 178428193, compound

HRID 1047578Notes

Reaction equation

HRID 1047578 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:32]=[CH:31][C:11]3[NH:12][C:13]([C:15]4[C:23]5[C:18](=[CH:19][CH:20]=[C:21]([NH2:24])[CH:22]=5)[N:17]([CH:25]5[CH2:30][CH2:29][CH2:28][CH2:27][O:26]5)[N:16]=4)=[N:14][C:10]=3[CH:9]=2)[CH2:4][CH2:3]1.N1(O)C2C=CC=CC=2N=N1.C(Cl)CCl.C(=O)(O)[O-].[Na+].[F:52][C:53]1([F:59])[CH2:55][CH:54]1[C:56](O)=[O:57]>CN(C=O)C>[F:52][C:53]1([F:59])[CH2:55][CH:54]1[C:56]([NH:24][C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][O:26]1)[N:16]=[C:15]2[C:13]1[NH:12][C:11]2[CH:31]=[CH:32][C:8]([N:5]3[CH2:6][CH2:7][CH:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:9][C:10]=2[N:14]=1)=[O:57]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27828232,2-Difluorocyclopropane-1-carboxylic acidHCID 178428192HCID 178428192, compound

Product 1

HCID 178428193HCID 178428193, compoundYield 56.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(5-(4-Methylpiperidin-1-yl)-1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine (50 mg, 0.116 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (HOBt) (23.54 mg, 0.174 mmol), EDC (33.4 mg, 0.174 mmol) and sodium bicarbonate (9.76 mg, 0.116 mmol) was added to a solution of 2,2-difluorocyclopropanecarboxylic acid (14.18 mg, 0.116 mmol) in DMF (6 mL). The reaction mixture was stirred at room temperature for 24 h, and the solvent was removed in vacuo. Purification by flash chromatography (6% CH3OH/CH2Cl2) afforded the title compound (35 mg). 1H NMR: (400 MHz, CD3OD): δ 8.49 (s, 1H), 7.75 (m, 1H), 7.66 (d, 1H, J=8.8 Hz), 7.54 (bs, 1H), 7.06 (m, 2H), 5.84 (dd, 1H, J=2.8 and 9.2 Hz), 3.96 (m, 1H), 3.80 (m, 1H), 3.58 (m, 2H), 2.69 (m, 4H), 2.11 (m, 3H), 1.82 (m, 4H), 1.70 (m, 2H), 1.49 (m, 1H), 1.41 (m, 2H), 0.99 (d, 3H, J=6.0 Hz); ESI-MS [M+H]+: 535.2.

Workup

  1. customthe solvent was removed in vacuo
  2. customPurification by flash chromatography (6% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-22b9315107754aa9b673395e51857298
Source dataset
uspto-grants-2013_10
Patent number
US08569511B2

Reaction notes

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