Diisopropylethylamine → HCID 86680041, compound

HRID 1915832Notes

Reaction equation

HRID 1915832 reaction equation
[CH3:1][O:2][CH:3]1[CH2:9][CH:8]=[C:7]([C:10]2[N:11]([CH3:18])[N:12]=[CH:13][C:14]=2[N+:15]([O-])=O)[CH2:6][CH2:5][CH:4]1[NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].CCN(C(C)C)C(C)C.[C:36]([O:40][C:41]([NH:43][C:44]1[S:48][C:47]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[F:55])=[N:46][C:45]=1[C:56]([OH:58])=O)=[O:42])([CH3:39])([CH3:38])[CH3:37].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.[F:85][P-](F)(F)(F)(F)F>CO.C(Cl)Cl.[Pd]>[C:36]([O:40][C:41]([NH:43][C:44]1[S:48][C:47]([C:49]2[C:54]([F:85])=[CH:53][CH:52]=[CH:51][C:50]=2[F:55])=[N:46][C:45]=1[C:56]([NH:15][C:14]1[CH:13]=[N:12][N:11]([CH3:18])[C:10]=1[CH:7]1[CH2:6][CH2:5][CH:4]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH:3]([O:2][CH3:1])[CH2:9][CH2:8]1)=[O:58])=[O:42])([CH3:37])([CH3:38])[CH3:39]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 674367135-((Tert-butoxycarbonyl)amino)-2-(2-fluorophenyl)thiazole-4-carboxylic acidHCID 86680042HCID 86680042, compound

Product 1

HCID 86680041HCID 86680041, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl N-(−2-methoxy-5-(2-methyl-4-nitro-pyrazol-3-yl)cyclohept-4-en-1-yl)carbamate (180 mg, 0.49 mmol) in MeOH (30 mL) was passed through the H-Cube® (full H2, 70° C., flow rate: 1 mL/min, 30 mm 20% Pd/C cartridge). The solvent was removed under reduced pressure to give a colourless oil. To a solution of this oil in DCM (30 mL) was added DIPEA (2.00 mL, 11.48 mmol) and 5-(tert-butoxycarbonylamino)-2-(2-fluorophenyl)thiazole-4-carboxylic acid (171 mg, 0.50 mmol) followed by PyBOP (596 mg, 1.15 mmol) and the mixture was stirred at room temperature for 16 hr. The reaction was quenched with water (20 mL) and extracted with DCM (80 mL). The organic layer was separated, dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel chromatography (70-80% EtOAc/isohexane) gave tert-butyl N-(5-(4-((5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carbonyl)amino)-2-methyl-pyrazol-3-yl]-2-methoxy-cycloheptyl]carbamate as a mixture of four diastereomers as an off-white solid (175 mg, 54% over two steps). 1H NMR (400 MHz, CDCl3) δ 10.39 and 10.36 (2s, 1H), 8.69 and 8.62 (2s, 1H), 8.32-8.28 and 8.21-8.14 (2 m, 1H), 7.85 and 7.75 (2s, 1H), 7.43-7.36 (m, 1H), 7.32 (t, J=7.6 Hz, 1H), 7.25-7.17 (m, 1H), 5.19 and 5.08 (2d, J=8.8 Hz, 1H), 3.84 (s, 3H), 3.78-3.54 (m, 2H), 3.37 and 3.27 (2s, 3H), 3.11-2.94 (m, 1H), 2.32-1.30 (m, 8H), 1.55 (s, 9H), 1.43 (s, 9H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto give a colourless oil
  3. customThe reaction was quenched with water (20 mL)
  4. extractionextracted with DCM (80 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customPurification via silica gel chromatography (70-80% EtOAc/isohexane)

Sources & evidence

ORD record
ord-e2322904a6d543b5923fc4651adb2556
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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