Ammonia → HCID 58529910, compound

HRID 1972814Notes

Reaction equation

HRID 1972814 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4[O:32][CH2:31][CH2:30][NH:29][CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH3:60][N:61]1[CH2:66]C[O:64][CH2:63][CH2:62]1.Cl.CN(C)CC(O)=O.C[O-].[Na+].N>C1COCC1.CO.C(Cl)Cl>[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4[O:32][CH2:31][CH2:30][N:29]([C:63](=[O:64])[CH2:62][N:61]([CH3:66])[CH3:60])[CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 6

HCID 222AmmoniaHCID 79724-MethylmorpholineHCID 75605N,N-Dimethylglycine hydrochlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10942334Sodium MethoxideHCID 58529811HCID 58529811, compound

Product 1

HCID 58529910HCID 58529910, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution in THF (1 mL) containing 5-(2-benzyl-2H-indazol-6-yl)-7-morpholin-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (170 mg, 0.315 mmol), (1H-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (209 mg, 0.47 mmol), N-methylmorpholine (111 mg, 1.1 mmol) and N,N-dimethylglycine hydrochloride (65.9 mg, 0.47 mmol) was stirred at rt for one hour. The reaction was diluted with 1 mL MeOH and treated with 25% sodium methoxide solution in MeOH (100 uL, 2 mmol). After an additional 30 min stirring at rt, the reaction was partitioned between EtOAc and 2N sodium carbonate solution. The organic phase was separated, dried with sodium sulfate and concentrated in vacuo to provide a dark orange solid. This material was taken up in 9.5 mL CH2Cl2 and 0.5 mL 7N NH3 in MeOH. The resulting solution was filtered through a silica plug (pretreated with NH3) and the volatiles removed in vacuo. Trituration of the resulting solid with ether provided 114 mg (71%) of the desired product as a tan solid. 1H NMR (300 MHz, DMSO-d6) δ 8.55 (s, 1 H), 7.98 (d, 1 H, J=4 Hz)), 7.60 (s, 1 H), 7.50-7.60 (m, 2H), 7.14 (d, 1H, J=7 Hz), 6.80 (s, 1H), 7.27-7.41 (m, 5H), 5.65 (s, 2H), 4.89-5.06 (m, 1H), 4.18-4.52 (m, 2H), 3.86-4.04 (m, 2H), 3.21-3.65 (m, 2H), 3.30 (s, 2H), 2.19 (s, 3H), 2.15 (s, 3H); ES-MS m/z 511.3 [M+H]+, HPLC RT (min) 2.12 min.

Workup

  1. stirringAfter an additional 30 min stirring at rt
  2. customthe reaction was partitioned between EtOAc and 2N sodium carbonate solution
  3. customThe organic phase was separated
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto provide a dark orange solid
  7. filtrationThe resulting solution was filtered through a silica plug (pretreated with NH3)
  8. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-e9a7f16579d348fd99902dfb31a83409
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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