Hydrochloric Acid → HCID 44481170, compound

HRID 1673257Notes

Reaction equation

HRID 1673257 reaction equation
C(OC([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16]([CH:18]=[CH:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([N:30]2[CH2:34][CH2:33][CH:32]([OH:35])[CH2:31]2)[C:27](O)=[O:28])=[CH:22][CH:21]=1)=[O:17])=O)(C)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH:69]1([C:72]2[CH:77]=[CH:76][C:75]([NH2:78])=[CH:74][CH:73]=2)[CH2:71][CH2:70]1.Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl.CO>[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:17])/[CH:18]=[CH:19]/[C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:27](=[O:28])[NH:78][C:75]2[CH:76]=[CH:77][C:72]([CH:69]3[CH2:71][CH2:70]3)=[CH:73][CH:74]=2)[N:30]2[CH2:34][CH2:33][C@H:32]([OH:35])[CH2:31]2)=[CH:22][CH:21]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733179PyBroPHCID 122539274-CyclopropylanilineHCID 66911499HCID 66911499, compound

Product 1

HCID 44481170HCID 44481170, compoundYield 20.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of {4-[2-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-vinyl]-phenyl}-(3-hydroxy-pyrrolidin-1-yl)-acetic acid (200 mg, 0.42 mmol), PyBroP (290 mg, 0.62 mmol) and DIPEA (162 mg, 1.26 mol) in CH2Cl2 (10 mL) was added 4-cyclopropyl-phenylamine (100 mg, 0.75 mmol). This mixture was stirred overnight at room temperature and then diluted with CH2Cl2 (20 mL), washed with saturated aqueous NaHCO3 solution, water and brine, dried with Na2SO4, and evaporated to obtain a yellow residue. Hydrochloric acid in methanol (1.25 M, 5 mL) was added to the residue, the mixture was stirred for about 3 h, and then NaHCO3 was added to the reaction system. After filtration of solids, the crude mixture was purified by preparative HPLC to obtain 42.3 mg pale-yellow solid. MS: calc'd 497 (MH+), exp 497 (MH+). 1H NMR (d4-MeOD, 400 MHz) 7.70 (m, 5H), 7.45 (m, 2H), 7.21 (m, 1H), 7.04 (m, 3H), 6.88 (m, 2H), 6.76 (m, 1H), 4.35 (m, 1H), 3.98(s, 1H, epimer A), 3.97 (s, 1H, epimer B), 3.00 (m, 1H), 2.56-1.85(m, 6H), 0.94(m, 2H), 0.64 (m, 2H).

Workup

  1. washwashed with saturated aqueous NaHCO3 solution, water and brine
  2. dry with materialdried with Na2SO4
  3. customevaporated
  4. customto obtain a yellow residue
  5. stirringthe mixture was stirred for about 3 h
  6. filtrationAfter filtration of solids
  7. customthe crude mixture was purified by preparative HPLC

Sources & evidence

ORD record
ord-dd76cce08273443dafa16f19595cf997
Source dataset
uspto-grants-2011_08
Patent number
US07999000B2

Reaction notes

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