Sodium cyanoborohydride → HCID 66711082, compound

HRID 1262130Notes

Reaction equation

HRID 1262130 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.[O:33]1[CH2:36][C:35](=O)[CH2:34]1.C([BH3-])#N.[Na+].N1N2C=CC=C2C=NC=1>CN(C)C=O.C(O)(=O)C.CO>[CH3:32][O:31][C:20]1[CH:21]=[C:22]([CH:25]2[CH2:30][CH2:29][N:28]([CH:35]3[CH2:36][O:33][CH2:34]3)[CH2:27][CH2:26]2)[CH:23]=[CH:24][C:19]=1[NH:18][C:15]1[N:14]=[CH:13][C:12]2=[CH:11][CH:10]=[C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])[N:17]2[N:16]=1

Participants

8

Reactant 4

HCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 21948608Pyrrolo[2,1-f][1,2,4]triazineHCID 66711490HCID 66711490, compound

Product 1

HCID 66711082HCID 66711082, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To [7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(2-methoxy-4-piperidin-4-yl-phenyl)-amine (60.00 mg, 0.140 mmol) in N,N-dimethylformamide (0.52 mL)/Methanol (2.00 mL)/Acetic acid (0.26 mL) was added oxetan-3-one (30.06 mg, 0.417 mmol) and the reaction mixture was cooled to 0° C. Sodium cyanoborohydride (43.64 mg, 0.695 mmol) was added and the reaction was heated at 60° C. overnight, and then at room temperature in air for 10 h to re-aromatize the pyrrolo[2,1-f][1,2,4]triazine core, which underwent partial reduction. The reaction mixture was concentrated, and the residue was partitioned between dichloromethane/1N sodium carbonate, washed with brine, dried over sodium sulfate, and concentrated. The product was isolated by flash chromatography (ISCO, SIlicagel, MeOH/DCM 0-10%) to afford [2-methoxy-4-(1-oxetan-3-yl-piperidin-4-yl)-phenyl]-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine as a yellow solid (40 mg, 59%). MP: 78-85° C.; 1H-NMR (CDCl3) δ 8.69 (s, 1H), 8.30 (d, J=8.7 Hz, 1H), 7.99 (dd, J=7.6 ; 1.4 Hz, 1H), 7.42 (m, 2H), 7.12 (m, 1H), 7.07 (d, J=8.4 Hz, 1H), 7.02 (d, J=4.6 Hz, 1H), 6.83 (d, J=4.6 Hz, 1H), 6.74 (m, 2H), 4.68 (m, 4H), 3.88 (s, 3H), 3.84 (s, 3H), 3.51 (m, 1H), 2.88 (m, 2H), 2.47 (m, 1H), 1.90 (m, 6H); LC/MS (ESI+): 485.9 (M+H).

Workup

  1. temperaturethe reaction was heated at 60° C. overnight
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was partitioned between dichloromethane/1N sodium carbonate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe product was isolated by flash chromatography (ISCO, SIlicagel, MeOH/DCM 0-10%)

Sources & evidence

ORD record
ord-4fd8206565e64e9185e62a4ef325fc16
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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