1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxypropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246656노트

반응식

HRID 246656 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:16]=[C:15]4[C:17]([C:20](O)=[O:21])=[CH:18][NH:19][C:14]4=[N:13][CH:12]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[NH2:23][C@@H:24]([CH3:27])[CH2:25][OH:26].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:16]=[C:15]4[C:17]([C:20]([NH:23][C@@H:24]([CH3:27])[CH2:25][OH:26])=[O:21])=[CH:18][NH:19][C:14]4=[N:13][CH:12]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 80307L-AlaninolHCID 81531DiisopropylethylamineHCID 712803892-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid

생성물 1

HCID 71279577(S)-2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxypropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide수율 26%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 2-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (200 mg, 0.638 mmol), (S)-2-aminopropan-1-ol (57 mg, 0.765 mmol), EDCI (366 mg, 1.914 mmol), HOBt (258 mg, 1.914 mmol) and DIPEA (247 mg, 1.914 mmol) in dry DMF (10 mL) was stirred for 16 hours at room temperature. Water (10 mL) was added, the formed precipitate was separated by filtration, washed with methanol (1 mL) then 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: 30% acetonitrile/70% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 60% acetonitrile/40% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min.) to afford (S)-2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxypropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (46 mg, 26% for two steps) as a yellow solid. LCMS: (M+H)+=371; 1H NMR (300 MHz, DMSO+D2O): δ 9.14 (s, 1H), 8.59 (d, 1H, J=8.7 Hz), 8.36 (s, 1H), 7.72 (s, 1H), 7.27 (dd, 1H, J1=8.4 Hz, J2=1.8 Hz), 4.23-4.18 (m, 1H), 3.55 (d, 1H, J=4.2 Hz), 1.25 (d, 1H, J=6.6 Hz).

후처리

  1. customthe formed precipitate was separated by filtration
  2. washwashed with methanol (1 mL)
  3. customthen was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  4. wait30% acetonitrile/70% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 60% acetonitrile/40% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min.

출처 및 근거

ORD 기록
ord-32e11ff6be7a40b1ad31fcac9ea26c15
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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