Dimethylformamide → HCID 56945615, compound

HRID 1262129Notes

Reaction equation

HRID 1262129 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:17]2[C:12]([CH:13]=[N:14][C:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[CH:21][C:20]=3[O:31][CH3:32])=[N:16]2)=[CH:11][CH:10]=1.C(OC([NH:40][C:41]([CH3:46])([CH3:45])[C:42](O)=[O:43])=O)(C)(C)C.Cl.CN(C)CCCN=C=NCC.CN(C)C=O>C([O-])(O)=O.[Na+]>[NH2:40][C:41]([CH3:46])([CH3:45])[C:42]([N:28]1[CH2:29][CH2:30][CH:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:15]3[N:14]=[CH:13][C:12]4=[CH:11][CH:10]=[C:9]([C:4]5[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=5[O:2][CH3:1])[N:17]4[N:16]=3)=[C:20]([O:31][CH3:32])[CH:21]=2)[CH2:26][CH2:27]1)=[O:43]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 66711490HCID 66711490, compound

Product 1

HCID 56945615HCID 56945615, compound

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

[7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(2-methoxy-4-piperidin-4-yl-phenyl)-amine (80.00 mg, 0.186 mmol), 2-tert-butoxycarbonylamino-2-methyl-propionic acid (0.045 g, 0.22 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.043 g, 0.22 mmol) and N,N-dimethylformamide (1.54 mL, 20.0 mmol) were combined in a round-bottom flask and stirred at room temperature overnight. The reaction mixture was diluted with saturated aqueous NaHCO3 and the resulting precipitate was collected by filtration and was washed twice with water, then dried under vacuum and used in the next step without further purification. Following the experimental procedure described in Example 787b), this precipitate was converted to 2-amino-1-(4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-2-methyl-propan-1-one as a yellow solid (58 mg, 61%). MP: 81-89° C.; 1H-NMR (CDCl3) δ 8.69 (s, 1H), 8.30 (d, J=8.8 Hz, 1H), 7.99 (dd, J=7.6; 1.6 Hz, 1H), 7.44 (m, 2H), 7.13 (m, 1H), 7.08 (d, J=8.4 Hz, 1H), 7.02 (d, J=4.7 Hz, 1H), 6.83 (d, J=4.7 Hz, 1H), 6.70 (m, 2H), 4.84 (m, 2H), 3.89 (s, 3H), 3.84 (s, 3H), 2.88 (m, 2H), 2.72 (m, 1H), 1.90 (m, 2H), 1.63 (m, 4H), 1.45 (s, 6H); LC/MS (ESI+): 515.0 (M+H).

Workup

  1. filtrationthe resulting precipitate was collected by filtration
  2. washwas washed twice with water
  3. customdried under vacuum
  4. customused in the next step without further purification

Sources & evidence

ORD record
ord-a2417a34feca4a729e96e2a6a10a706f
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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