Hydrochloric Acid → HCID 178478933、化合物

HRID 246619ノート

反応式

HRID 246619 の反応式
[F:1][CH:2]([F:40])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([C:23]([NH:25][C@@H:26]3[CH2:31][CH2:30][C@H:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28][CH2:27]3)=[O:24])=[CH:21][NH:20][C:17]2=[N:18][CH:19]=1.[ClH:41]>O1CCOCC1>[ClH:41].[NH2:32][C@@H:29]1[CH2:28][CH2:27][C@H:26]([NH:25][C:23]([C:22]2[C:16]3=[N:15][C:14]([C:7]4[C:6]5[C:10](=[CH:11][CH:12]=[C:4]([O:3][CH:2]([F:1])[F:40])[CH:5]=5)[N:9]([CH3:13])[N:8]=4)=[CH:19][N:18]=[C:17]3[NH:20][CH:21]=2)=[O:24])[CH2:31][CH2:30]1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 178481759HCID 178481759、化合物

生成物 1

HCID 178478933HCID 178478933、化合物収率 29.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
25 °C

実験手順

tert-Butyl cis-4-(2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)cyclohexylcarbamate (54 mg, 0.1 mmol) in 3 mL of 1,4-dioxane was added 10 mL of concentrated HCl. The reaction mixture was stirred overnight at 25° C. After evaporation under the reduced pressure, the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min). After concentration, the crude solid was treated with 1N HCl (2 mL), the mixture was stirred for 10 min then evaporated and dried to afford N-(cis-4-aminocyclohexyl)-2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide hydrochloride (13 mg, 29.5%) as yellow solid. LCMS: (M+H)+=456; 1H NMR (300 MHz, CD3OD): δ 8.96 (s, 1H), 8.22 (s, 1H), 8.01 (d, 1H, J=2.1 Hz), 7.56 (d, 1H, J=9.0 Hz), 7.26 (dd, 1H, J1=9.0 Hz, J2=2.4 Hz), 6.76 (t, 1H, J=74.1 Hz), 4.16-4.14 (m, 1H), 4.11 (s, 3H), 3.17-3.15 (m, 1H), 2.15-2.11 (m, 2H), 1.91-1.78 (m, 4H), 1.60-1.48 (m, 2H).

後処理

  1. customAfter evaporation under the reduced pressure
  2. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min
  4. concentrationAfter concentration
  5. additionthe crude solid was treated with 1N HCl (2 mL)
  6. stirringthe mixture was stirred for 10 min
  7. customthen evaporated
  8. customdried

出典と根拠

ORDレコード
ord-f67a042efe8743b5a7f84b580a1db2ae
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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