Boron Trichloride → (Z)-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(prop-1-enyl)pyrimidin-2-yl)thiophene-2-sulfonamide

HRID 1484946Notes

Reaction equation

HRID 1484946 reaction equation
B(Cl)(Cl)Cl.C([NH:9][S:10]([C:13]1[S:14][C:15]([C:18]2[N:23]=[C:22]([NH:24][C:25]3[CH:29]=[C:28]([CH:30]4[CH2:32][CH2:31]4)[NH:27][N:26]=3)[C:21](/[CH:33]=[CH:34]\[CH3:35])=[CH:20][N:19]=2)=[CH:16][CH:17]=1)(=[O:12])=[O:11])(C)(C)C>C(Cl)Cl>[CH:30]1([C:28]2[NH:27][N:26]=[C:25]([NH:24][C:22]3[C:21](/[CH:33]=[CH:34]\[CH3:35])=[CH:20][N:19]=[C:18]([C:15]4[S:14][C:13]([S:10]([NH2:9])(=[O:12])=[O:11])=[CH:17][CH:16]=4)[N:23]=3)[CH:29]=2)[CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 25135Boron TrichlorideHCID 58169526(Z)-N-tert-butyl-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(prop-1-enyl)pyrimidin-2-yl)thiophene-2-sulfonamide

Product 1

HCID 50943692(Z)-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(prop-1-enyl)pyrimidin-2-yl)thiophene-2-sulfonamideYield 77.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

BCl3 (1 M in CH2Cl2, 3.28 mL, 3.28 mmol, 4.0 equiv.) was added to a stirred solution of (Z)—N-tert-butyl-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(prop-1-enyl)pyrimidin-2-yl)thiophene-2-sulfonamide (375.6 mg, 0.82 mmol, 1.0 equiv.) in CH2Cl2 (20 mL) at room temperature under nitrogen. The reaction mixture was stirred for 30 min and then quenched with aq. NaHCO3 in ice bath. The reaction mixture was extracted with ethyl acetate and washed with water, brine, dried and evaporated. The crude product was crystallized with THF/isopropyl to afford (Z)-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(prop-1-enyl)pyrimidin-2-yl)thiophene-2-sulfonamide (Compound 207) (255.1 mg, 77.4%). LC-MS (m/z)=403 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.75-0.76 (m, 2H), 0.95-1.00 (m, 2H), 1.79-1.81 (m, 2H), 1.90 (d, J=6.0 Hz, 1H), 1.93-1.97 (m, 1H), 5.60-6.04 (m, 0.6H), 6.26-6.31 (m, 0.4H), 6.46-6.49 (s, 1.5H), 6.79 (d, J=15.2 Hz, 0.4H), 7.57-7.59 (m, 1H), 7.74-7.79 (m, 3H), 8.19 (s, 0.6H), 8.39 (s, 0.4H), 8.94 (s, 0.5H), 9.33 (s, 0.3H).

Workup

  1. customquenched with aq. NaHCO3 in ice bath
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. washwashed with water, brine
  4. customdried
  5. customevaporated
  6. customThe crude product was crystallized with THF/isopropyl

Sources & evidence

ORD record
ord-986747048dcc4768ad6c759d1b592e47
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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