Diisopropylethylamine → HCID 86679966, compound

HRID 1915755Notes

Reaction equation

HRID 1915755 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][N:5]([CH2:22][CH:23]([F:25])[F:24])[C:6]=1[N:7]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]([CH3:21])[C:15](=[O:20])[C:16]([F:19])([F:18])[F:17])[CH2:9][CH2:8]1.CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Br:68][C:69]1[S:70][C:71]([NH:77][C:78]([O:80][C:81]([CH3:84])([CH3:83])[CH3:82])=[O:79])=[C:72]([C:74](O)=[O:75])[N:73]=1>C(Cl)Cl.O>[Br:68][C:69]1[S:70][C:71]([NH:77][C:78](=[O:79])[O:80][C:81]([CH3:83])([CH3:82])[CH3:84])=[C:72]([C:74](=[O:75])[NH:1][C:2]2[CH:3]=[N:4][N:5]([CH2:22][CH:23]([F:25])[F:24])[C:6]=2[N:7]2[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]([CH3:21])[C:15](=[O:20])[C:16]([F:18])([F:17])[F:19])[CH2:9][CH2:8]2)[N:73]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 581821562-Bromo-5-((tert-butoxycarbonyl)amino)thiazole-4-carboxylic acidHCID 86679967Acetamide, N-[(4R)-1-[4-amino-1-(2,2-difluoroethyl)-1H-pyrazol-5-yl]hexahydro-1H-azepin-4-yl]-2,2,2-trifluoro-N-methyl-

Product 1

HCID 86679966HCID 86679966, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)—N-(1-(4-amino-1-(2,2-difluoroethyl)-1H-pyrazol-5-yl)azepan-4-yl)-2,2,2-trifluoro-N-methylacetamide (248 mg, 0.67 mmol) in DCM (20 mL) was added DIPEA (1.0 mL, 5.7 mmol), PyBOP (700 mg, 1.34 mmol) and 2-bromo-5-(tert-butoxycarbonylamino)-thiazole-4-carboxylic acid (282 mg, 0.87 mmol) and the mixture was stirred at room temperature for 20 hr. Water (50 mL) was added and stirring continued for 1 hr. The mixture was extracted with DCM (50 mL), the combined organic layers were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave (R)-tert-butyl 2-bromo-4-(1-(2,2-difluoroethyl)-5-(4-(2,2,2-trifluoro-N-methylacetamido)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate as a pale yellow gum (405 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 10.27 and 10.26 (2s, 1H), 8.32 and 8.27 (2s, 1H), 7.88 and 7.85 (2s, 1H), 6.36-6.02 (m, 1H), 4.67-4.11 (m, 2H), 3.41-3.08 (m, 5H), 3.08 and 2.95 (2s, 3H), 2.22-1.71 (m, 4H), 1.31-1.18 (m, 2H).

Workup

  1. stirringstirring
  2. waitcontinued for 1 hr
  3. extractionThe mixture was extracted with DCM (50 mL)
  4. customthe combined organic layers were passed through a phase separation cartridge
  5. customthe solvent removed under reduced pressure
  6. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-1a31673f22f845c2b9c9ce7b4cb5ccd1
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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