Trifluoroacetic acid → N-({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-1-inden-yl]-amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)sulfamide

HRID 1397558Notes

Reaction equation

HRID 1397558 reaction equation
[NH2:1][S:2]([N:5]([CH2:13][C@@H:14]1[CH2:18][C@@H:17]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C@@H:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH3:37])[N:23]=[CH:22][N:21]=2)[CH2:16][C@@H:15]1[OH:38])C(=O)OC(C)(C)C)(=[O:4])=[O:3].FC(F)(F)C(O)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[OH:38][C@H:15]1[CH2:16][C@H:17]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C@@H:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH3:37])[N:23]=[CH:22][N:21]=2)[CH2:18][C@H:14]1[CH2:13][NH:5][S:2]([NH2:1])(=[O:4])=[O:3]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66797857tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

Product 1

HCID 59671425N-({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-1-inden-yl]-amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)sulfamideYield 84.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]cyclopentyl}-methyl)carbamate (34.5 mg, 0.0000628 mol) in CH2Cl2 (1.4 mL) was added trifluoroacetic acid (0.70 mL, 0.0091 mol) and the mixture was stirred for 15 minutes. The mixture was diluted with toluene and evaporated to dryness. The residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2) to obtain 23.8 mg (84%) of the title compound as a white residue. 1H NMR (CD3OD, 400 MHz) δ: 8.15 (s, 1H), 7.24-7.14 (m, 4H), 5.98 (s, 1H), 5.57 (bs, 1H), 5.29 (bs, 1H), 4.38-4.35 (m, 1H), 4.23-4.20 (m, 1H), 3.34 (s, 3H), 3.25-3.20 (m, 1H), 3.13-3.00 (m, 3H), 2.42-2.33 (m, 1H), 2.29-2.24 (m, 1H), 2.10-1.94 (m, 3H) ppm. LC/MS: Rt=1.16 min, ES+ 450 (FA standard).

Workup

  1. customevaporated to dryness
  2. customThe residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-60e12745a06a49598a5221c5dbdb6e82
Source dataset
uspto-grants-2014_12
Patent number
US08901136B2

Reaction notes

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