Hydrochloric Acid → Capivasertib

HRID 422984노트

반응식

HRID 422984 반응식
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([NH:13][C:14]([C:16]2([NH:31]C(=O)OC(C)(C)C)[CH2:21][CH2:20][N:19]([C:22]3[C:23]4[CH:30]=[CH:29][NH:28][C:24]=4[N:25]=[CH:26][N:27]=3)[CH2:18][CH2:17]2)=[O:15])[CH2:10][CH2:11][OH:12])=[CH:5][CH:4]=1>ClCCl>[NH2:31][C:16]1([C:14]([NH:13][C@H:9]([C:6]2[CH:5]=[CH:4][C:3]([Cl:2])=[CH:8][CH:7]=2)[CH2:10][CH2:11][OH:12])=[O:15])[CH2:17][CH2:18][N:19]([C:22]2[C:23]3[CH:30]=[CH:29][NH:28][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:20][CH2:21]1

참가 물질

4

반응물 2

HCID 313Hydrochloric AcidHCID 57750298(S)-tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate2회

생성물 1

HCID 25227436Capivasertib수율 19.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
20 °C

실험 절차

HCl (4M in Dioxane) (3.00 mL, 12.00 mmol) was added to (S)-tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 22) (1.27 g, 2.40 mmol) in dichloromethane (20 mL). The resulting suspension was stirred at 20° C. for 16 hours. The reaction mixture was filtered through a PTFE filtercup and the crude solid was purified by preparative HPLC (Waters XTerra C18 column, 5 μm silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% TFA) and MeCN as eluents. Fractions containing the desired compound were purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (0.200 g, 19.4%) as a white solid. 1H NMR (399.9 MHz, DMSO-d6) δ 1.45 (2H, d), 1.86 (1H, d), 1.90-1.93 (1H, m), 2.19 (2H, s), 3.38 (2H, q), 3.51-3.58 (2H, m), 4.35-4.38 (2H, m), 4.53 (1H, t), 4.88 (1H, d), 6.58 (1H, t), 7.16 (1H, t), 7.32-7.38 (4H, m), 8.12 (1H, s), 8.43 (1H, d), 11.63 (1H, s), m/z (ESI+) (M+H)+=429; HPLC tR=1.46 min.

후처리

  1. filtrationThe reaction mixture was filtered through a PTFE filtercup
  2. customthe crude solid was purified by preparative HPLC (Waters XTerra C18 column, 5 μm silica, 19 mm diameter, 100 mm length)
  3. additionFractions containing the desired compound
  4. customwere purified by ion exchange chromatography
  5. washThe desired product was eluted from the column
  6. customwere evaporated to dryness

출처 및 근거

ORD 기록
ord-93267d51893140d7af5711e2e9799e10
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101623B2

반응 노트

불러오는 중…