Methanesulfonamide → HCID 71002230, compound

HRID 2402402Notes

Reaction equation

HRID 2402402 reaction equation
[OH:1][C@:2]1([C:15]2[S:16][C:17]([C:20]3[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([NH:27][C:28]4[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][N:29]=4)[N:21]=3)=[CH:18][N:19]=2)[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([OH:14])=O)[CH:5]=[CH:4][C:3]1=2.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[OH:1][C@:2]1([C:15]2[S:16][C:17]([C:20]3[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([NH:27][C:28]4[CH:33]=[C:32]([C:34]([F:37])([F:35])[F:36])[CH:31]=[CH:30][N:29]=4)[N:21]=3)=[CH:18][N:19]=2)[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([NH:42][S:39]([CH3:38])(=[O:41])=[O:40])=[O:14])[CH:5]=[CH:4][C:3]1=2

Participants

6

Reactant 4

HCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70977851(R)-5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid

Product 1

HCID 71002230HCID 71002230, compoundYield 97.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of (R)-5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (20 mg, 0.038 mmol) and methanesulfonamide (4.34 mg, 0.046 mmol) in DCM (2 mL) at rt was added HATU (28.9 mg, 0.076 mmol) followed by Hunig's base (0.040 mL, 0.228 mmol) and the mixture was stirred at rt for 16 h. The solvent was removed under reduced pressure, and the residue was purified by reverse phase HPLC using a C18 column and a solvent system of MeCN and water modified with 0.1% TFA. The product-containing fractions were collected and lyophilized to give (R)-5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-N-(methylsulfonyl)-5,6,7,8-tetrahydronaphthalene-2-carboxamide (22.4 mg, 82%) as light yellow solid. MS ESI calcd for C27H24F3N5O4S2 [M+H]+ 604, found 604. 1H NMR (500 MHz, dmso) δ 10.21 (s, 1H), 8.65 (s, 1H), 8.48 (s, 1H), 8.22 (d, J=3.9, 1H), 7.74 (s, 1H), 7.69-7.61 (m, 1H), 7.39-7.29 (m, 2H), 7.26-7.17 (m, 1H), 7.10 (s, 1H), 3.34 (s, 3H), 2.87 (m, 2H), 2.40-2.32 (m, 2H), 2.30 (s, 3H), 2.17-2.06 (m, 1H), 2.05-1.88 (m, 1H) ppm.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by reverse phase HPLC
  3. customThe product-containing fractions were collected

Sources & evidence

ORD record
ord-bb87822606b145d2b3f41f591a09c5e9
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

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