Diisopropylethylamine → HCID 86680024, compound

HRID 1915817Notes

Reaction equation

HRID 1915817 reaction equation
C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Br:34][C:35]1[S:36][C:37]([NH:43]C(OC(C)(C)C)=O)=[C:38]([C:40]([OH:42])=O)[N:39]=1.[NH2:51][C:52]1[CH:53]=[N:54][N:55]([CH3:73])[C:56]=1[N:57]1[CH2:63][CH2:62][CH:61]([F:64])[CH:60]([NH:65][C:66](=[O:72])[O:67][C:68]([CH3:71])([CH3:70])[CH3:69])[CH2:59][CH2:58]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[NH2:43][C:37]1[S:36][C:35]([Br:34])=[N:39][C:38]=1[C:40]([NH:51][C:52]1[CH:53]=[N:54][N:55]([CH3:73])[C:56]=1[N:57]1[CH2:63][CH2:62][CH:61]([F:64])[CH:60]([NH:65][C:66](=[O:72])[O:67][C:68]([CH3:69])([CH3:70])[CH3:71])[CH2:59][CH2:58]1)=[O:42]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 581821562-Bromo-5-((tert-butoxycarbonyl)amino)thiazole-4-carboxylic acidHCID 86680025HCID 86680025, compound

Product 1

HCID 86680024HCID 86680024, compoundYield 111.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of PyBOP (3.06 g, 5.03 mmol) and 2-bromo-5-(tert-butoxycarbonyl-amino)thiazole-4-carboxylic acid (1.63 g, 5.04 mmol) in DCM (50 mL) was stirred at room temperature for 15 min. tert-Butyl 1-(4-amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-ylcarbamate (1.37 g, 4.20 mmol) and DIPEA (1.17 mL, 6.71 mmol) were added and the mixture stirred at room temperature for 2 days. The reaction mixture was diluted with DCM (50 mL) and washed with water (3×50 mL). The organic layers was passed through a phase separation cartridge and concentrated under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% EtOAc/isohexane) gave tert-butyl 1-(4-(5-amino-2-bromothiazole-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-ylcarbamate as a pink solid (2.50 g, 94%). 1H NMR (400 MHz, CDCl3) δ 10.27 (s, 1H), 8.27 (s, 1H), 7.64 (s, 1H), 5.01 (s, 1H), 4.86-4.60 (m, 1H), 3.81-3.64 (m, 3H), 3.44-3.27 (m, 2H), 3.15-3.07 (m, 2H), 2.28-2.10 (m, 3H), 1.92-1.70 (m, 2H), 1.52 (s, 9H), 1.44 (s, 9H).

Workup

  1. additionwere added
  2. washwashed with water (3×50 mL)
  3. customThe organic layers was passed through a phase separation cartridge
  4. concentrationconcentrated under reduced pressure
  5. customPurification of the residue via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-f71d026d838d497c8dbd629cc335a0f3
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

Loading…