Sodium cyanoborohydride → N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(1,3-oxazol-2-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 529820

반응식

HRID 529820 반응식
[NH2:1][CH2:2][CH2:3][N:4]1[CH:8]=[C:7]([NH:9][C:10]([C:12]2[CH:13]=[N:14][N:15]3[CH:20]=[CH:19][CH:18]=[N:17][C:16]=23)=[O:11])[C:6]([C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=2[O:28][CH:29]([F:31])[F:30])=[N:5]1.[O:32]1[CH:36]=[CH:35][N:34]=[C:33]1[CH:37]=O.[BH3-]C#N.[Na+]>CO>[Cl:27][C:25]1[CH:24]=[CH:23][C:22]([O:28][CH:29]([F:30])[F:31])=[C:21]([C:6]2[C:7]([NH:9][C:10]([C:12]3[CH:13]=[N:14][N:15]4[CH:20]=[CH:19][CH:18]=[N:17][C:16]=34)=[O:11])=[CH:8][N:4]([CH2:3][CH2:2][NH:1][CH2:37][C:33]3[O:32][CH:36]=[CH:35][N:34]=3)[N:5]=2)[CH:26]=1

참가 물질

5

반응물 3

HCID 5003444Sodium cyanoborohydrideHCID 147866091,3-Oxazole-2-carboxaldehydeHCID 118522637N-[1-(2-aminoethyl)-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

생성물 1

HCID 118522737N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(1,3-oxazol-2-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide수율 45.3%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

To a solution of N-[1-(2-aminoethyl)-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (100 mg, 0.22 mmol) in MeOH (15 mL) was added 1,3-oxazole-2-carbaldehyde (21.7 mg, 0.22 mmol), followed by NaBH3CN (16 mg, 0.25 mmol). The resulting solution was stirred at room temperature for 12 h. The resulting mixture was concentrated under vacuum. The residue was passed through a short pad of silica gel eluting with 5% MeOH in DCM. The crude product was purified by Prep-HPLC with the following conditions (2#-AnalyseHPLC-SHIMADZU(HPLC-10)): Column, XBridge BEH130 Prep C18 OBD Column, 19� 100 mm 5 um 13 nm; mobile phase, Water with 10 mM NH4CO3 and ACN (20% ACN up to 50% in 6 min); Detector, UV 254/220 nm. 52.7 mg product was obtained. This resulted in 52.7 mg (45%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(1,3-oxazol-2-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid. LCMS (Method 20) [M+H]+=529.2, RT=2.42 min. 1H NMR (300 MHz, CD3OD-d4) δ: (ppm) 9.08 (dd, 1H, J=1.7, 7.1 Hz), 8.66-8.63 (m, 2H), 8.34 (s, 1H), 7.87 (d, 1H, J=0.6 Hz), 7.67 (d, 1H, J=2.7 Hz), 7.53 (dd, 1H, J=2.4, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.19 (dd, 1H, J=4.2, 7.2 Hz), 7.13 (d, 1H, J=0.6 Hz), 6.55 (t, 1H, J=73.5 Hz), 4.33 (t, 2H, J=6.0 Hz), 3.95 (s, 2H), 3.14 (t, 2H, J=6.0 Hz).

후처리

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product was purified by Prep-HPLC with the following conditions (2#-AnalyseHPLC-SHIMADZU(HPLC-10))
  3. waitmobile phase, Water with 10 mM NH4CO3 and ACN (20% ACN up to 50% in 6 min)

출처 및 근거

ORD 기록
ord-5f41dfb180ce4b128e47a55008c06114
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346815B2

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