Methanesulfonamide → 2-(4-{5-fluoro-4-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}-1H-pyrazol-1-yl)-N-(methylsulfonyl)acetamide

HRID 2362681Notes

Reaction equation

HRID 2362681 reaction equation
[F:1][C:2]1[C:3]([C:20]2[S:24][C:23]([C:25]3([OH:29])[CH2:28][CH2:27][CH2:26]3)=[N:22][CH:21]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]([OH:19])=O)[CH:15]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[CH3:30][S:31]([NH2:34])(=[O:33])=[O:32].Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CN(C)C1C=CN=CC=1.CS(C)=O>[F:1][C:2]1[C:3]([C:20]2[S:24][C:23]([C:25]3([OH:29])[CH2:28][CH2:27][CH2:26]3)=[N:22][CH:21]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]([NH:34][S:31]([CH3:30])(=[O:33])=[O:32])=[O:19])[CH:15]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 670037172-(4-(5-fluoro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-pyrazol-1-yl)acetic acid

Product 1

HCID 670035762-(4-{5-fluoro-4-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}-1H-pyrazol-1-yl)-N-(methylsulfonyl)acetamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 2-(4-(5-fluoro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-pyrazol-1-yl)acetic acid (Example 65B) (75 mg, 0.181 mmol) in N,N-dimethylformamide (1.0 mL) was added methanesulfonamide (20.7 mg, 0.218 mmol), 4-dimethylaminopyridine (66.5 mg, 0.544 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (52.2 mg, 0.272 mmol). The solution was heated to 45° C. for 4 hours. The reaction was cooled to room temperature and diluted with dimethyl sulfoxide (1 mL). The resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 um column, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v trifluoroacetic acid and B is acetonitrile containing 0.1% v/v trifluoroacetic acid) to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 12.35 (s, 1H), 12.30-12.18 (m, 1H), 8.43 (s, 1H), 8.35 (s, 1H), 8.22 (d, J=3.6 Hz, 1H), 8.16 (s, 1H), 7.07 (d, J=2.0 Hz, 1H), 6.67 (s, 1H), 5.10 (s, 2H), 3.29 (s, 3H), 2.64-2.56 (m, 2H), 2.46-2.32 (m, 2H), 2.05-1.87 (m, 2H); MS ESI(+) m/z 490.9 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 um column
  3. washeluting with a gradient of 5% B in A to 75% B in A over 25 minutes

Sources & evidence

ORD record
ord-77435665fa0d42928be76be0ce9b2b80
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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