Cyclobutanol → HCID 57926010, compound

HRID 1013472Notes

Reaction equation

HRID 1013472 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)=[CH:11][C:10]=1[NH:20][C:21]([C:23]1[CH:33]=[CH:32][C:26]([CH2:27][P:28]([CH3:31])(=[O:30])[OH:29])=[CH:25][CH:24]=1)=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:34]1(O)[CH2:37][CH2:36][CH2:35]1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[CH:34]1([O:30][P:28]([CH2:27][C:26]2[CH:25]=[CH:24][C:23]([C:21](=[O:22])[NH:20][C:10]3[CH:11]=[C:12]([C:15]4[S:16][CH:17]=[CH:18][CH:19]=4)[CH:13]=[CH:14][C:9]=3[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[CH:33][CH:32]=2)([CH3:31])=[O:29])[CH2:37][CH2:36][CH2:35]1

Participants

6

Reactant 4

HCID 76218CyclobutanolHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 57925981HCID 57925981, compound

Product 1

HCID 57926010HCID 57926010, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [4-(2-tert-butoxycarbonylamino-5-thiophen-2-yl-phenylcarbamoyl)-benzyl]-methyl-phosphinic acid (57 mg, 0.117 mmol), cyclobutanol (0.038 mL, 0.703 mmol), and Hunig's Base (0.031 mL, 0.176 mmol) in DMF (2 mL) was added BOP (78 mg, 0.176 mmol). After 18 h, the reaction was purified by preparative HPLC Reverse phase (C-18), eluting with acetonitrile/water plus 0.025% TFA (40-100%) to give material after extraction of fractions with EtOAc. 1H NMR (DMSO-d6) δ 9.88 (s, 1H), 8.74 (br s, 1H), 7.90 (d, J=7.6 Hz, 2H), 7.79 (br s, 1H), 7.58 (d, J=8.5 Hz, 1H), 7.52-7.47 (m, 2H), 7.44-7.39 (m, 3H), 7.12-7.09 (m, 1H), 4.64 (m, 1H), 3.27 (dd, J=23.2, 17.6 Hz, 1H), 3.25 (dd, J=23.2, 17.6 Hz, 1H), 2.25-21.4 (m, 2H), 2.05-1.94 (m, 2H), 1.67-1.60 (m, 1H), 1.49-1.42 (m, 1H), 1.43 (s, 9H), 1.31 (d, J=14.1 Hz, 3H). MS: cal'd 441 (MH+; -Boc), exp 441 (MH+; -Boc).

Workup

  1. customthe reaction was purified by preparative HPLC Reverse phase (C-18)
  2. washeluting with acetonitrile/water plus 0.025% TFA (40-100%)
  3. customto give material
  4. extractionafter extraction of fractions with EtOAc

Sources & evidence

ORD record
ord-463a7517cf774cef81d08c9224dff930
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

Loading…