tert-Butyl 4-ethynylpiperidine-1-carboxylate → HCID 67347390, compound

HRID 1676316Notes

Reaction equation

HRID 1676316 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:19](C2C=CC(F)=CC=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[C:35]([CH:37]1[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]1)#[CH:36]>>[C:25]([C:22]1([C:20]([NH:19][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[CH:14]=[CH:13][N:12]=[C:11]4[CH:15]=[C:16]([C:36]#[C:35][CH:37]5[CH2:38][CH2:39][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:41][CH2:42]5)[S:17][C:10]=34)=[C:2]([F:1])[CH:3]=2)=[O:21])[CH2:23][CH2:24]1)(=[O:26])[NH2:27]

Participants

3

Reactant 2

HCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylateHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 67347390HCID 67347390, compound

Procedure

Prepared from N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 350 mg, 0.592 mmol) and tert-butyl 4-ethynylpiperidine-1-carboxylate (186 mg, 0.888 mmol) using the procedure described for Example 6, Step B. The crude was purified by Biotage Flash 40M eluting with 20% EtOAc/hexanes (500 mL), 1:1 EtOAc/hexanes (1 L), followed by 2:1 EtOAc/hexanes (1.5 L). The product was isolated as a wax (293 mg, 68%). HPLC: 92% purity (254 nm); LRMS (APCI+): m/z 673, 573 (loss of BOC) (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 10.12 (s, 1H), 8.47 (d, J=6 Hz, 1H), 8.33 (s, 1H), 7.77 (m, 1H), 7.44 (m, 2H), 7.25 (m, 3H), 7.06 (t, J=9 Hz, 2H), 6.50 (d, J=6 Hz, 1H), 3.77 (m, 2H), 3.23 (m, 2H), 2.87 (m, 1H), 1.89 (m, 2H), 1.80 (m, 2H), 1.70 (m, 2H), 1.62 (m, 2H), 1.47 (s, 9H).

Workup

  1. customThe crude was purified by Biotage Flash 40M
  2. washeluting with 20% EtOAc/hexanes (500 mL), 1:1 EtOAc/hexanes (1 L)
  3. customThe product was isolated as a wax (293 mg, 68%)

Sources & evidence

ORD record
ord-052ce397a84244ae8032b2ef2d2172c9
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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