Dichloromethane → (3R,3aR,6S,6aR)-N6-[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diamine 2,2,2-trifluoroacetic acid

HRID 929232Notes

Reaction equation

HRID 929232 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:22](COCC[Si](C)(C)C)[C:21]([NH:31][C@H:32]3[CH2:36][O:35][C@@H:34]4[C@H:37]([NH:40]C(=O)OC(C)(C)C)[CH2:38][O:39][C@H:33]34)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.C(Cl)Cl.[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52]>CO>[F:54][C:53]([F:56])([F:55])[C:51]([OH:57])=[O:52].[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([NH:31][C@@H:32]3[C@H:33]4[O:39][CH2:38][C@@H:37]([NH2:40])[C@H:34]4[O:35][CH2:36]3)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 131735103tert-butyl N-[(3S,3aR,6R,6aR)-3-[[6-chloro-5-(4-phenylphenyl)-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]amino]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]carbamate

Product 1

HCID 118413248(3R,3aR,6S,6aR)-N6-[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diamine 2,2,2-trifluoroacetic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Tert-butyl N-[(3S,3aR,6R,6aR)-3-[[6-chloro-5-(4-phenylphenyl)-1-(2-trimethylsilylethoxy-methyl)imidazo[4,5-b]pyridin-2-yl]amino]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]carbamate (1.1 mg, 0.0016 mmol) was dissolved in TFA (0.2 mL) and DCM (0.5 mL) and stirred at room temperature for 1 hour. Then the reaction mixture was evaporated to give an oil, which was dissolved in methanol (0.5 mL) and purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water+0.05% TFA gradient. The desired fractions were lyophilized to give the title compound as a solid. Major isomer LC-MS: calculated for C24H22ClN5O2 447.15 observed m/e: 448.24 (M+H)+ (Rt 0.96/2 min); 1H NMR δ (ppm) (CD3OD): 7.82 (s, 1H), 7.76 (ABq, 4H), 7.71 (d, 2H), 7.49 (dd, 2H), 7.39 (dd, 1H), 4.90 (m, 1H), 4.79 (d, 1H), 4.52 (br d, 1H), 4.28 (dd, 1H), 4.20-4.12 (m, 2H), 3.96 (m, 1H) and 3.82 (dd, 1H).

Workup

  1. customThen the reaction mixture was evaporated
  2. customto give an oil, which
  3. custompurified by preparative HPLC reverse phase (C-18)
  4. washeluting with a 20%-80% acetonitrile/water+0.05% TFA gradient

Sources & evidence

ORD record
ord-7288dc9311e448e5a2777e7726952d82
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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