Hydrochloric Acid → HCID 58790047, compound

HRID 2193799Notes

Reaction equation

HRID 2193799 reaction equation
[NH2:1][C:2]1[CH:32]=[CH:31][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:17]=[N:18][C:19](=[O:30])[N:20]([CH2:22][CH2:23][N:24]5[CH2:29][CH2:28][O:27][CH2:26][CH2:25]5)[CH:21]=4)[S:15][C:8]=23)=[C:4]([F:33])[CH:3]=1.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[NH:42][C:43](=[O:48])[CH2:44][C:45](O)=[O:46].C1C=CC2N(O)N=NC=2C=1.Cl>CN(C=O)C.C(Cl)CCl>[F:33][C:4]1[CH:3]=[C:2]([NH:1][C:45](=[O:46])[CH2:44][C:43]([NH:42][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[O:35][CH3:34])=[O:48])[CH:32]=[CH:31][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:17]=[N:18][C:19](=[O:30])[N:20]([CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[CH:21]=3)[S:15][C:8]=12

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 12664594N-(2-Methoxy-phenyl)-malonamic acidHCID 587901415-(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-(2-morpholinoethyl)pyrimidin-2(1H)-one

Product 1

HCID 58790047HCID 58790047, compoundYield 13.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the amine 416 (0.16 mmol) in DMF (1 mL) was added acid 27 (38 mg, 0.18 mmol), HOBT (24 mg, 0.18 mmol) and EDC×HCl (46 mg, 0.24 mmol). The mixture was stirred at room temperature for 16 h. The solvent was evaporated, then the residue was purified by flash chromatography with gradient of methanol (0-5%) in dichloromethane, followed by preparative HPLC purification with gradient of methanol (20-100%) in water to give title compound 412 (14 mg, 13% yield). MS (m/z): 659.1 (M+H). 1H NMR (DMSO-d6) δ (ppm): 10.59 (s, 1H), 9.64 (s, 1H), 9.16 (d, J=3.3 Hz, 1H), 8.69 (d, J=3.3 Hz, 1H), 8.51 (d, J=5.5 Hz, 1H), 8.07 (d, J=7.4 Hz, 1H), 7.98 (s, 1H), 7.88 (dd, J=13.2.3 Hz, 1H), 7.51 (t, J=9.0 Hz, 1H), 7.43 (dd, J=8.8, 1.6 Hz, 1H), 7.11-7.05 (m, 2H), 6.94-6.90 (m, 1H), 6.67 (d, J=4.7 Hz, 1H), 4.05 (t, J=6.5 Hz, 2H), 3.86 (s, 3H), 3.64 (s, 2H), 3.55-3.50 (m, 4H), 2.63 (t, J=5.5 Hz, 2H), 2.46-2.42 (m, 4H).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by flash chromatography with gradient of methanol (0-5%) in dichloromethane
  3. customfollowed by preparative HPLC purification with gradient of methanol (20-100%) in water

Sources & evidence

ORD record
ord-4030383d228640cd967e8b43ddb37c83
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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