Water → HCID 66698258, compound

HRID 1256580Notes

Reaction equation

HRID 1256580 reaction equation
[F:1][CH:2]([F:35])[C:3]1[N:7]([C:8]2[N:13]=[C:12]3[N:14]([CH:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[N:15]=[CH:16][C:11]3=[C:10]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[C:32]([O:33][CH3:34])[C:5]=2[N:4]=1.CCN(C(C)C)C(C)C.Cl[CH2:46][CH2:47][S:48](Cl)(=[O:50])=[O:49].O>C(Cl)Cl>[F:35][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]3[N:14]([CH:17]4[CH2:22][CH2:21][N:20]([S:48]([CH:47]=[CH2:46])(=[O:50])=[O:49])[CH2:19][CH2:18]4)[N:15]=[CH:16][C:11]3=[C:10]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[C:32]([O:33][CH3:34])[C:5]=2[N:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 15385Ethanesulfonylchloride, 2-chloro-HCID 81531DiisopropylethylamineHCID 67543644HCID 67543644, compound

Product 1

HCID 66698258HCID 66698258, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

A mixture of 0.41 g (0.84 mmol) of 6-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-4-(4-morpholinyl)-1-(4-piperidinyl)-1H-pyrazolo[3,4-d]pyrimidine (Example 8) and 0.27 g (2 mmol) DIPEA in CH2Cl2 was cooled to −15° C., and 200 mg (1.2 mmol) of 2-chloroethanesulfonyl chloride was added. The mixture was allowed to warm to 0° C. over 1 hr, and water was added. The organic layer was dried and concentrated. Chromatography on silica, eluting with CH2Cl2/EtOAc (1:1), gave 216 mg (45% yield) of 6-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-4-(4-morpholinyl)-1-[1-(vinylsulfonyl)-4-piperidinyl]-1H-pyrazolo[3,4-d]pyrimidine: mp (CH2Cl2-MeOH) 243-246° C.; 1H NMR (CDCl3) δ 8.00 (s, 1H), 7.81 (dd, J=8.4, 0.7 Hz, 1H), 7.44 (t, JHF=53.5 Hz, 1H), 7.37 (t, J=8.2 Hz, 1H), 6.82 (d, J=7.7 Hz, 1H), 6.51 (dd, J=16.6, 9.9 Hz, 1H), 6.29 (d, J=16.6 Hz, 1H), 6.07 (d, J=9.9 Hz, 1H), 4.81 (tt, J=11.2, 4.1 Hz, 1H), 4.07 (s, 3H), 4.06 (m, 4H), 3.96 (m, 1H), 3.91 (m, 4H), 3.88 (m, 1H), 2.95 (dt J=12.4, 2.6 Hz, 2H), 2.43 (ddd, J=24.5, 11.8, 4.2 Hz, 2H), 2.14 (dd, J=11.8, 4.2 Hz, 2H); Anal. Calcd. for C25H28F2N8O4S: C, 52.3; H, 4.9; N, 19.5. Found: C, 52.3; H, 4.7; N, 19.8%.

Workup

  1. temperatureto warm to 0° C. over 1 hr
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. washChromatography on silica, eluting with CH2Cl2/EtOAc (1:1)

Sources & evidence

ORD record
ord-d9b6b2b296e84cc785c7d15acb3b8f4b
Source dataset
uspto-grants-2013_06
Patent number
US08461158B2

Reaction notes

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