tert-butyl 2((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate → 9-cyclopentyl-N-(5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 2200070Notes

Reaction equation

HRID 2200070 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:25]=[CH:24][C:23]5[CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19][C:18]=5[N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:33]=[CH:34][N:35]=[CH:36][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:25]=[CH:24][C:23]5[CH2:22][NH:21][CH2:20][CH2:19][C:18]=5[N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:33]=[CH:34][N:35]=[CH:36][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

3

Reactant 1

HCID 68313968tert-butyl 2((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

Product 1

HCID 665496459-cyclopentyl-N-(5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineYield 86%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of tert-butyl 2((9-cyclopentyl-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (217 mg, 0.477 mmol) in TFA/DCM (1:1, 2 mL) was stirred at room temperature for 30 minutes and then concentrated. The residue was purified by flash chromatography on silica gel eluting with 25% to 75% solvent A (DCM:MeOH:NH4OH, 100:10:1) in DCM to give the title compound as a yellow solid (148 mg, 86% yield). 1H NMR (500 MHz, CDCl3) δ 1.87-1.90 (2H, m), 2.14-2.21 (4H, m), 2.43-2.47 (2H, m), 2.89 (2H, t, J=5.0 Hz), 3.26 (2H, t, J=5.0 Hz), 4.02 (2H, s), 5.36 (1H, m), 7.41 (1H, d, J=10.0 Hz), 7.85 (1H, d, J=5.0 Hz), 8.19 (1H, br. s), 8.31 (1H, d, J=10.0 Hz), 8.52 (1H, d, J=5.0 Hz), 8.91 (1H, s), 9.11 (1H, s) ppm; LCMS m/z: 386 (M+1).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by flash chromatography on silica gel eluting with 25% to 75% solvent A (DCM:MeOH:NH4OH, 100:10:1) in DCM

Sources & evidence

ORD record
ord-6030b9cf27b148d194db9d4d0b435304
Source dataset
uspto-grants-2016_06
Patent number
US09359355B2

Reaction notes

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