Dimethylformamide → HCID 11562615, compound

HRID 347570Notes

Reaction equation

HRID 347570 reaction equation
C(OC([CH2:8][CH2:9][NH:10][C:11]1[CH:12]=[C:13]([C:25]([OH:27])=O)[C:14](=[O:24])[N:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH:16]=1)=O)(C)(C)C.Cl.Cl.[F:30][C:31]1[CH:32]=[C:33]([NH:58]C(NC(=O)CC2C=CC(F)=CC=2)=S)[CH:34]=[CH:35][C:36]=1[O:37][C:38]1[C:43]2=[C:44]([CH3:57])C(OCCN3CCN(C)CC3)=CN2N=CN=1.CN([P+](ON1N=[N:90][C:85]2[CH:86]=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C([N:101]([CH2:104]C)CC)C.C[N:107](C=O)C>O>[NH:101]1[C:104]2=[N:90][CH:85]=[CH:86][C:38]([O:37][C:36]3[CH:35]=[CH:34][C:33]([NH:58][C:25]([C:13]4[C:14](=[O:24])[N:15]([C:17]5[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=5)[CH:16]=[C:11]([NH:10][CH2:9][CH2:8][NH2:107])[CH:12]=4)=[O:27])=[CH:32][C:31]=3[F:30])=[C:43]2[CH:44]=[CH:57]1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 21081693HCID 21081693, compoundHCID 1317262361-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4] triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, bis-hydrochloride salt2×

Product 1

HCID 11562615HCID 11562615, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 5-(2-(tert-butoxycarbonyl)ethylamino)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (50 mg, 0.13 mmol) and 4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorobenzenamine (40 mg, 0.16 mmol, Compound B of Example 132), BOP reagent (100 mg, 0.23 mmol) in DMF (1 mL) was stirred at 50° C. with triethylamine (0.1 mL) for 1 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with methylene chloride (3×10 mL). The combined organic extracts were washed with water, dried and concentrated in vacuo. The residue was stirred with TFA (1 mL) at room temperature for 30 minutes. The TFA was removed and the residue was purified by preparative HPLC. The fraction containing the desired product was collected and concentrated in vacuo. The residue was converted to the HCl salt by adding 1 N HCl solution and lyophilizing to give the title compound (20 mg, 27%). 1H NMR (CD3OD) δ 8.35 (d, 1H, J=2.6 Hz), 8.26 (d, 1H, J=5.5 Hz), 8.01 (dd, 1H, J=10.4, 2.6 Hz), 7.48 (m, 2H), 7.41 (m, 6H), 6.81 (d, 1H, J=5.5 Hz), 6.60 (s, 1H), 3.26 (t, 2H, J=6.1 Hz), 3.07 (t, 2H, J=6.1 Hz); MS(ESI+) m/z 517 (M+H)+.

Workup

  1. extractionextracted with methylene chloride (3×10 mL)
  2. washThe combined organic extracts were washed with water
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe TFA was removed
  6. customthe residue was purified by preparative HPLC
  7. additionThe fraction containing the desired product
  8. customwas collected
  9. concentrationconcentrated in vacuo
  10. additionby adding 1 N HCl solution

Sources & evidence

ORD record
ord-18fd8e827b834afd955a2ca9e694c35b
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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