Water → Azd-6088

HRID 1642468Notes

Reaction equation

HRID 1642468 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]2([CH3:26])[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH2:11][CH2:10]1.Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(C(C)C)CC)(C)C.O>ClCCl>[O:30]=[C:28]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]3([CH3:26])[CH2:16][CH2:17][N:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:19][CH2:20]3)[CH2:11][CH2:10]2)[C@H:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]2[NH:1]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 44541147ethyl 4-[4-[[(1S,2S)-2-aminocyclohexyl]amino]-1-piperidyl]-4-methyl-piperidine-1-carboxylate

Product 1

HCID 25221108Azd-6088Yield 61.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of ethyl 4-[4-[[(1S,2S)-2-aminocyclohexyl]amino]-1-piperidyl]-4-methyl-piperidine-1-carboxylate (87 mg, 0.24 mmol) in dichloromethane (5 mL) was added with triphosgene (0.1 mmol) at 0° C. followed by with diisopropylethyl amine (0.5 mmol) and stirred at room temperature for 12 h. Water (2 mL) was added followed by dichloromethane (20 mL), the phases were separated and the aqueous phase was extracted with dichloromethane (2×10 mL). The combined organic phases were washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product, which was purified with preparative LC/MS (high pH) to give the title compound as white solid 24 mg (25%). 1H NMR (400 MHz, METHANOL-D4) δ ppm 0.96 (s, 3H), 1.22 (t, J=7.08 Hz, 3H), 1.31-1.49 (m, 6H), 1.55-1.63 (m, 1H), 1.66-1.87 (m, 7H), 1.91-1.99 (m, 2H), 2.08-2.22 (m, 2H), 2.24-2.31 (m, 1H), 2.89-3.10 (m, 4H), 3.33-3.43 (m, 2H), 3.45-3.53 (m, 2H), 3.54-3.63 (m, 1H), 4.08 (q, J=7.08 Hz, 2H). MS (M+1): 393.3.

Workup

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with dichloromethane (2×10 mL)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give the crude product, which
  7. customwas purified with preparative LC/MS (high pH)

Sources & evidence

ORD record
ord-2b9db79b0ea3439fb37b93cf90bc9c8c
Source dataset
uspto-grants-2012_02
Patent number
US08119661B2

Reaction notes

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