1,2-Dichloroethane → HCID 178429875, compound

HRID 1047573Notes

Reaction equation

HRID 1047573 reaction equation
[CH3:1][CH:2]1[CH2:7][N:6]([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)[CH2:5][CH2:4][O: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:6]3[CH2:5][CH2:4][O:3][CH:2]([CH3:1])[CH2:7]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 178429874HCID 178429874, compound

Product 1

HCID 178429875HCID 178429875, compoundYield 64.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(5-(2-Methylmorpholino)-1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine (20 mg, 0.046 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (9.37 mg, 0.069 mmol), EDC (13.30 mg, 0.069 mmol) and sodium bicarbonate (3.88 mg, 0.046 mmol) was added to a solution of 2,2-difluorocyclopropanecarboxylic acid (5.64 mg, 0.046 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 (16 mg) as a solid. 1H NMR: (400 MHz, CD3OD): δ 8.51 (s, 1H), 7.75-7.65 (m, 2H), 7.56 (m, 1H), 7.04 (m, 2H), 5.84 (dd, 1H, J=2.4 and 9.6 Hz), 3.98 (m, 2H), 3.80 (m, 3H), 3.51 (m, 1H), 3.43 (m, 1H), 2.77 (m, 2H), 2.60 (m, 1H), 2.11 (m, 3H), 1.85 (m, 2H), 1.70 (m, 2H), 1.23 (d, 3H, J=6.0 Hz); ESI-MS [M+H]+: 537.1.

Workup

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

Sources & evidence

ORD record
ord-999f0bde25b34623923fd55fec370d46
Source dataset
uspto-grants-2013_10
Patent number
US08569511B2

Reaction notes

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