Water → 3-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1888538Notes

Reaction equation

HRID 1888538 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[N:10]1([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:24]=[C:25]([C:30]4[CH:35]=[CH:34][N:33]=[CH:32][C:31]=4[NH2:36])[C:26](F)=[N:27][CH:28]=3)=[CH:19][CH:18]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.O>C1COCC1>[N:10]1([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[N:27][C:26]4[NH:36][C:31]5[CH:32]=[N:33][CH:34]=[CH:35][C:30]=5[C:25]=4[CH:24]=3)=[CH:19][CH:18]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 962WaterHCID 3280088Npc316347HCID 582665135-(4-Piperidin-1-ylmethyl-phenyl)-2-fluoro-[3,4']bipyridinyl-3'-ylamine

Product 1

HCID 582664053-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrroleYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1N solution of bis(trimethylsilyl)amide in THF (2.78 mL, 2.80 mmol) was added dropwise to a solution of 5-(4-piperidin-1-ylmethyl-phenyl)-2-fluoro-[3,4′]bipyridinyl-3′-ylamine (101 mg, 0.278 mmol) in THF (5.0 mL) at ambient temperature. The mixture was stirred for 1 h at ambient temperature and then treated with water. The resultant brown solution was partitioned between DCM and water, the layers separated, and the aqueous phase extracted into 20% methanol in DCM. The combined organic phase was concentrated in vacuo. The resultant residue was absorbed onto silica gel, and purified by flash chromatography (silica, 1-20% methanol in DCM) to provide a light orange-yellow solid (39.9 mg, 42%). 1H NMR (DMSO-D6, 500 MHz): 12.24 (s, 1H), 8.99 (d, J=1.8 Hz, 1H), 8.93 (s, 1H), 8.92 (d, J=1.8 Hz, 1H), 8.45 (d, J=5.2 Hz, 1H), 8.22 (d, J=5.2 Hz, 1H), 7.77 (d, J=7.5 Hz, 2H), 7.45 (d, J=7.5 Hz, 2H), 3.49 (s, 2H), 2.36 (m, 4H), 1.52 (m, 4H), 1.41 (m, 2H). LCMS (Method D): RT=4.64 min, M+H+=343.

Workup

  1. customThe resultant brown solution was partitioned between DCM and water
  2. customthe layers separated
  3. extractionthe aqueous phase extracted into 20% methanol in DCM
  4. concentrationThe combined organic phase was concentrated in vacuo
  5. customThe resultant residue was absorbed onto silica gel
  6. custompurified by flash chromatography (silica, 1-20% methanol in DCM)

Sources & evidence

ORD record
ord-67fa35a6b1064a888a1457e7f0a765fa
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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