1,2-Dichloroethane → N-(3-(1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)-2,2-difluorocyclopropanecarboxamide

HRID 1047539Notes

Reaction equation

HRID 1047539 reaction equation
[F:1][C:2]1([F:8])[CH2:4][CH:3]1[C:5](O)=[O:6].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(=O)(O)[O-].[Na+].[NH:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=[C:29]1[C:37]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43]([NH2:46])[CH:44]=2)[N:39]([CH:47]2[CH2:52][CH2:51][CH2:50][CH2:49][O:48]2)[N:38]=1>CN(C=O)C>[NH:30]1[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[N:28]=[C:29]1[C:37]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43]([NH:46][C:5]([CH:3]3[CH2:4][C:2]3([F:8])[F:1])=[O:6])[CH:44]=2)[N:39]([CH:47]2[CH2:52][CH2:51][CH2:50][CH2:49][O:48]2)[N:38]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27828232,2-Difluorocyclopropane-1-carboxylic acidHCID 1363522453-(1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine

Product 1

HCID 136352252N-(3-(1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)-2,2-difluorocyclopropanecarboxamideYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,2-Difluorocyclopropanecarboxylic acid (8 mg, 0.065 mmol), HOBt (12 mg, 0.089 mmol), EDC (17 mg, 0.089 mmol) and sodium bicarbonate (56 mg, 0.059 mmol) were added to a solution of 3-(1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine (20 mg, 0.059 mmol) in DMF (6 mL). The reaction mixture was stirred at room temperature for 24 h, and then the solvent was removed in vacuo. Purification by flash chromatography (6% CH3OH/CH2Cl2) afforded the title compound as a solid in a 50% yield. 1H NMR (400 MHz, CD3OD): δ 8.51 (s, 1H), 7.77 (m, 1H), 7.67 (m, 3H), 7.27 (m, 2H), 5.86 (d, 1H, J=7.6 Hz), 4.00 (m, 1H), 3.81 (m, 1H), 2.74-2.61 (m, 2H), 2.13 (m, 3H), 1.84 (m, 2H), 1.69 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-bf4eeae49e0b46b3a8b61d41f3b1b272
Source dataset
uspto-grants-2013_10
Patent number
US08569511B2

Reaction notes

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