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 1747611Notes

Reaction equation

HRID 1747611 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-cedce32e1c30400aa82c071ac385671f
Source dataset
uspto-grants-2015_10
Patent number
US09150525B2

Reaction notes

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